Heterodimerization

Cry2 is a blue-light photoreceptor cryptochrome from Arabidopsis used as a light-responsive multi-component optogenetic switch. The supplied evidence supports blue-light-dependent photoactivation linked to regulation of transcription factor control and to CRY2 degradation.

CRY2/CIB1 is a blue-light-inducible multi-component interaction switch composed of the photoreceptor CRY2 and its interacting partner CIB1. It is used for acute light-dependent protein recruitment, including plasma-membrane recruitment and clustering, to control protein localization and downstream signaling with high spatial and temporal resolution.

EL222 is a blue light-activated LOV-HTH transcription factor from the marine bacterium Erythrobacter litoralis HTCC2594 that functions as a light-dependent DNA-binding protein for optical control of transcription. Its flavin mononucleotide chromophore photodynamics have been characterized in free solution and when embedded in EL222 variants.

iLID/SspB is a blue-light-inducible heterodimerization system built from an engineered iLID module and the SspB binding partner. It is used to reversibly recruit proteins in cells for control of localization and signaling, including membrane recruitment, neurotrophin receptor construction, microtubule plus-end targeting, and perturbation of small GTPase pathways.

PhyB/PIF is a genetically encoded red/far-red light-inducible dimerization system built from phytochrome B and phytochrome-interacting factor. It enables reversible light-controlled protein association and dissociation on the second time scale and has been applied to gene regulation, protein transport, and subcellular recruitment.

OptoRAF1 is a blue light-responsive optogenetic RAF1 system built on the CRY2/CIB1 dimerizer pair. It reversibly activates the RAF/MEK/ERK pathway by recruiting RAF1 to the plasma membrane.

Magnets are engineered pairs of distinct light-responsive protein modules derived from the Neurospora crassa photoreceptor Vivid. They act as a multi-component optogenetic switch by converting a native Vivid homodimerization interface into complementary light-dependent heterodimers for protein interaction and recruitment in subcellular volumes.

The split Cas9 logic gate is a synthetic multi-component circuit that uses split Cas9 halves to sense biological events through conditional reconstitution of Cas9 activity. In the reported 2023 implementation, self-assembling inteins reconstituted split Cas9 and enabled reporter activation only when specified transcriptional or cell-state inputs were present.

Light Activated BioID (LAB) is an optically controlled proximity-labeling system in which the two halves of split-TurboID are fused to the photodimerizing proteins CRY2 and CIB1. Blue light induces CRY2–CIB1 association, reconstituting split-TurboID and enabling proximity-dependent biotinylation of nearby proteins.

Drug-inducible lentiviral and transposon vectors were used to deliver the PhyB-PIF light-inducible dimerization system together with the synPCB phycocyanobilin synthesis module. In the cited study, doxycycline treatment induced PCB synthesis and enabled PhyB-PIF light-inducible dimerization function.

Biofunctional nanodot arrays (bNDAs) are nanoscale surface-patterned delivery harnesses designed to spatially control dimerization and clustering of cell-surface receptors. In live cells, they were used to capture extracellularly GFP-tagged Lrp6 and drive assembly of active Wnt signalosomes at the plasma membrane.

Cry2/CIB is a genetically encoded blue-light-activated protein dimerization module derived from Arabidopsis thaliana. It is used to optically induce protein-protein interactions and has been applied to control transcription, protein localization, protein secretion, and, when coupled to BAX, light-triggered apoptosis.

The iLID N414L variant is a modified iLID light-inducible dimerization system in which an N414L point mutation in the LOV domain lengthens the reversion half-life. In combination with SspB binding partners, it supports blue-light-dependent control of protein colocalization and has been used in reengineered iLID-SspB systems for processes including transmembrane protein localization.

LOVpep/ePDZb is a blue-light-inducible heterodimerization system examined as one of three optogenetic dimer variants in a comparative cellular optogenetics study. It mediates light-dependent protein association that was used to control cellular localization and activity in assays including transcription, intracellular localization, and GTPase signaling.

OptoBAX is an optimized light-activated Cry2-BAX multi-component optogenetic system developed for one-click initiation of the BAX-mediated apoptotic cascade. It is used to trigger outer mitochondrial membrane permeabilization and induce early apoptotic events with light.

YF1 is an engineered light-oxygen-voltage (LOV) histidine kinase that acts as a blue-light-regulated signaling switch. Available evidence indicates that blue-light input is transmitted through structural transitions in the photosensor and linker regions that control its signaling state.

CRISPR-dCas9 was used in an optogenetic LITE configuration to control endogenous PIM1 transcription in U87 glioblastoma cells in vitro. In this study, the system mediated light-inducible, reversible transcriptional induction or repression rather than genome editing.

The light-switchable condensate system is a genetically encoded, multi-component platform for blue light-controlled organization of functional cargoes in Escherichia coli. It couples a condensation-enabling scaffold to cargo proteins through the iLID/SspB light-responsive interaction pair to dynamically regulate cargo localization.

Venus iLID is an optogenetic improved Light Inducer Dimer system used to impose light-controlled protein proximity. In the cited application, a Venus iLID-based strategy was developed to bring αvβ3 integrin and ALK3 into proximity, and this was sufficient to induce cell spreading on a soft substrate.

Inducible, engineered myeloid precursors (iRANK cells) treated with a chemical inducer of dimerization (CID) differentiated into TRAP+ multinucleated OCs and resorbed mineralized tissues in vitro.

iLID-nano is a multi-component optogenetic switch built from an improved light-induced dimerization pair comprising LOV2-SsrA and SspB. It has been used to control talin-mediated cell spreading and migration and has been physically characterized for force-coupled regulation in mechanotransduction contexts.

Opto-RhoGEFs are optogenetically recruitable Rho guanine nucleotide exchange factor systems for light-controlled, reversible regulation of Rho GTPase activity. In a 2023 eLife study, they were used to control endothelial cell morphology and vascular endothelial barrier strength from global to subcellular scales.

Finally, we developed a chemically inducible version of GFE3, chGFE3, which degrades inhibitory synapses when combined with the bio-orthogonal dimerizer HaloTag ligand-trimethoprim.

De novo tripeptides composed of glycine, tyrosine, and lysine were reported to generate cyan fluorescence in vitro. The same study further indicates that amino acid identity and residue order modulate the fluorescent output, and that these peptides form robust dimer structures under moderate oxidizing conditions.

Galpha(15i3) is a G protein chimera reported in HEK293 cells as a pathway-linking component that couples the sweet taste receptor heterodimer TAS1R2/TAS1R3 to an InsP3-dependent Ca2+ release pathway. It is described together with Galpha(16gust44) in receptor signaling assays.

Galpha(16gust44) is a G protein chimera used in HEK293 cells as part of a multi-component signaling switch. It couples the sweet taste receptor heterodimer TAS1R2/TAS1R3 to an InsP3-dependent intracellular Ca2+ release pathway.

Membrane-tethered CRY2 is a CRY2/CIB optical dimerization configuration in which CRY2 is localized at a membrane to control recruitment of CIB-linked partners with light. The reported application demonstrates that this arrangement is functional and may provide improved local control of protein interactions.

The split transcriptional activator based gluconate switch is a multi-component mammalian gene-control system derived from the Escherichia coli gluconate-responsive regulator GntR. It uses gluconate-induced GntR dimerization to reconstitute a split transcriptional activator and activate transgene expression.

Using this synthetic SAC (SynSAC) approach

TULIPs is an optical dimerizer system benchmarked as a multi-component light-controlled switch for regulating protein interactions in yeast. In the cited comparison, it produced a transcriptional response similar to CRY2/CIB1 and was evaluated in assays relevant to transcription and MAPK signaling control.

BcWCL1 PASΔ is a PAS-domain-deleted variant of the Botrytis cinerea blue-light photoreceptor BcWCL1 that functions in yeast as a blue-light-activated transcription switch. The reported activity depends on the BcWCL1 N-terminal region, which supports light-stimulated self-dimerization and contains a functional 9aaTAD-family transcriptional activation domain.

MagMboI is a photoactivatable split version of the type II restriction endonuclease MboI configured as a multi-component switch for light-controlled nuclease function. The supplied evidence indicates that an optimized variant, MagMboI-plus, produced stronger genome rearrangement activity than the original MagMboI in Saccharomyces cerevisiae.

Our predictions guided the engineering of four variants (R20A, R22A, D103A, and R20A-R22A), all of which impaired GAL-7-induced apoptosis in human T cells.

The iLID-SspB A58V variant is a blue-light-inducible heterodimerization system in which SspB carries a single A58V substitution. It was reengineered to tune iLID-SspB binding for improved light-controlled protein colocalization, including transmembrane protein localization in neurons.

AQTrip is an engineered EL222 variant carrying V41I, L52I, A79Q, and V121I substitutions in the blue-light-responsive LOV–HTH transcription factor. It stabilizes the photoactivated state and, in the reported study, oligomerizes without DNA and forms an EL222 dimer–DNA complex in the presence of DNA substrates.

The AUREO1 bZIP-LOV truncated construct (ZL) is an N-terminally truncated aureochrome-1 derivative that retains the bZIP DNA-binding region and the LOV photosensory domain. It binds DNA in a sequence-specific manner and undergoes a blue-light-induced conformational response measurable as an approximately 5% increase in hydrodynamic radius without a detectable change in secondary structure.

BcLOV4-ARHGEF11 is a single-transgene optogenetic fusion in which the upstream RhoA activator ARHGEF11 is fused to BcLOV4. It enables light-inducible, spatiotemporally precise control of RhoA signaling through dynamic membrane localization without requiring a separate protein binding partner.

The BcLOV4-RhoA optogenetic fusion is a single-transgene light-responsive construct in which RhoA GTPase, or its upstream activator ARHGEF11, is fused to BcLOV4. It enables spatiotemporally precise optical control of RhoA signaling and associated cytoskeletal and mechanotransductive responses without requiring a separate protein binding partner for dynamic membrane localization.

The blue light-activated PKC isozyme recruitment system is a multi-component optogenetic switch that uses the plant-derived CRY2-CIB1 interaction to recruit PKC isozyme catalytic domains to the cell surface under blue light. In the reported format, CRY2-tagged PKC catalytic domains undergo light-triggered membrane translocation, and a PKCε implementation robustly activates GIRK1/4 potassium channels.

The C120 promoter is a TAEL-responsive regulatory element used in the zebrafish TAEL optogenetic transcription system. Blue light induces TAEL transcription factor dimerization, which activates transcription from the C120 promoter.

CluMPS (Clusters Magnified by Phase Separation) is a fluorescent reporter strategy for high-sensitivity detection of protein clusters in cells. It is reported to visualize submicroscopic clusters, including small aggregates, and to track clusters of unmodified, tagged, and endogenous proteins.

CreLite is an optogenetically controlled Cre/loxP recombination system reported in developing zebrafish embryos. It uses split Cre recombinase halves fused to the red light-inducible partners PhyB and PIF6, so that 660 nm illumination in the presence of phycocyanobilin (PCB) restores Cre activity.

The CRY2-CIB1 interaction system is a blue-light-responsive optogenetic multi-component switch built from the light-inducible CRY2-CIB1 interaction system in mammalian cells. Photoexcited CRY2 supports inducible CRY2-CIB1 heterodimerization and can also undergo concomitant CRY2-CRY2 homo-oligomerization, enabling light-controlled manipulation of signaling pathways and cellular processes with high spatiotemporal precision.

The CRY2-CRY2 interaction system is a blue-light-responsive optogenetic switch in which photoexcited cryptochrome 2 undergoes homo-oligomerization. In mammalian cells, this light-inducible interaction has been used to manipulate signaling pathways and cellular processes with high spatiotemporal precision.

The CRY2-talin/CIBN-CAAX optogenetic plasma membrane recruitment system is a blue-light-responsive two-component switch that fuses Arabidopsis cryptochrome 2 to the N terminus of full-length talin and anchors the N-terminal cryptochrome-interacting basic helix-loop-helix domain to the plasma membrane with a CAAX motif. In Chinese hamster ovary cells and endothelial cells, 450 nm illumination recruits talin to the plasma membrane and promotes activation of β3 integrins, including αIIbβ3- and αVβ3-associated complexes.

The CRY2/CIBN light-gated dimerizer system is an optogenetic multi-component switch used to control subcellular RhoA activation through light-dependent recruitment of a CRY2-fused RhoA activator. In the cited implementation, the ARHGEF11 DHPH catalytic domain is fused to CRY2-mCherry to drive light-gated relocalization and thereby modulate force-related cellular phenotypes.

FerriTag is a genetically encoded, chemically inducible tag for correlative light-electron microscopy built as a fluorescent, electron-dense ferritin particle. It labels target proteins through induced heterodimerization and enables nanoscale localization in electron micrographs.

The FKF1/GIGANTEA light-inducible transcription system is an optogenetic multi-component switch for mammalian cells built from the Arabidopsis photoreceptor FKF1 and its binding partner GIGANTEA. In an optimized split FKF1/GI dimerized Gal4-VP16 configuration, light induces transcriptional activation by reconstituting a functional transcriptional regulator.

The full-length AUREO1 construct is a blue-light-responsive transcription factor from Vaucheria frigida that contains an N-terminal bZIP domain and a C-terminal LOV domain. In the reported study, the full-length protein binds DNA in a sequence-specific manner and undergoes an approximately 5% blue-light-induced increase in hydrodynamic radius.

Fusion proteins with large N-terminal anchors are an anchor-design variant for the light-inducible iLID recruitment system. In this configuration, the modified anchor supports light-controlled recruitment of components to subcellular locations, including micron-scale regions of the plasma membrane, to improve control of protein localization and signaling outputs.

The genetically encodable, light activatable heterodimerizer system is an optogenetic multi-component switch that places a protein cargo within a genetically encoded, light-responsive heterodimerization framework. In the cited application, incorporation of cofilin enabled illumination-dependent remodeling of the F-actin network and consequent changes in cell motility.

iLID-RTK is a blue-light-controlled, multi-component receptor tyrosine kinase switch built from the iLID and tdnano system. In darkness it is cytosolic, monomeric, and inactive, while blue light recruits two iLID-RTK molecules to tdnano to drive RTK dimerization and activation.

LACE is a light-activated CRISPR/Cas9 effector system that induces transcription of endogenous genes in the presence of gene-specific guide RNAs and blue light. It functions as a multi-component optical switch for programmable gene activation and has also been used to spatially pattern reporter expression under photomask illumination.

LADL (light-activated dynamic looping system) is a multi-component optogenetic genome-engineering platform that targets two genomic anchors with CRISPR guide RNAs and promotes their spatial co-localization through light-induced heterodimerization between CRY2 and dCas9-CIBN. In the cited 2018 study, this engineered looping altered endogenous gene expression, including increased nascent Zfp462 transcription and increased synchronous Sox2 expression.

Light inducible dimer pairs are multicomponent optogenetic switches derived from cyanobacteriochrome photoswitchable proteins. They enable light-dependent heterodimerization and were developed to support orthogonal control of biological processes with red, green, and blue light.

Opto-RGS2 is an optogenetic multi-component switch that uses a light-induced heterodimerization system to recruit the RGS2 domain to the plasma membrane, where it interacts with its cognate G protein. It was developed to enable optical control of Gq-protein signaling and associated calcium oscillation dynamics.

LINTAD is a multi-component light-inducible nuclear translocation and dimerization system developed for gene regulation. In the cited study, it was used to control chimeric antigen receptor (CAR) T-cell activation, and pulsed light stimulation activated LINTAD-engineered CAR T cells to produce strong cytotoxicity against target cancer cells in vitro and in vivo.

Light-inducible TrkA activation strategies comprise four engineered optical designs for activating TrkA signaling without nerve growth factor. The reported approaches use light to drive plasma membrane recruitment and homo-interaction of the intracellular domain of TrkA, recapitulating native NGF/TrkA-associated functions.

The LightOn system is an optogenetic gene-expression switch in which blue light induces activity of the GAVPO regulator to control expression of a gene of interest. In the cited 2023 work, all LightOn components were assembled into the OPTO-BLUE lentiviral platform for light-controlled reporter expression.

The near-infrared light-activated DNA agonist nanodevice (NIR-DA) is a multicomponent, nongenetic system for remote optical control of receptor tyrosine kinase signaling in live cells and animals. Upon near-infrared illumination, an active DNA agonist is released and dimerizes DNA-modified chimeric or native receptor tyrosine kinases at the cell surface, triggering downstream signaling.

opto-Dab1 is a single-component, photoactivatable version of Disabled-1 (Dab1) created by exploiting the blue light-sensitive dimerization/oligomerization properties of Arabidopsis thaliana Cryptochrome 2 (Cry2). Upon blue light illumination, it enables rapid, local, and reversible activation of Dab1 downstream signaling.

Optogenetic protein kinase A is a light-controlled multi-component switch for probing localized protein kinase A signaling. It uses the Cry2-Cib photodimerizing pair to translocate a low-constitutive-activity protein kinase A catalytic subunit to a Cib-defined subcellular site, where kinase activity is restored.

Optogenetic split transcription factors are multi-component light-responsive transcriptional regulators developed in Saccharomyces cerevisiae. In the cited yeast toolkit, split transcription factor designs incorporated cryptochrome and Enhanced Magnet light-sensitive dimerizers, and an optimized Enhanced Magnet variant improved light-sensitive gene expression.

OptoMYPT is a blue-light-controlled multi-component optogenetic switch that couples the PP1c-binding domain of MYPT1 to an optogenetic dimerizer to recruit endogenous protein phosphatase 1c to the plasma membrane. This recruitment induces dephosphorylation of myosin regulatory light chains and reduces actomyosin contractile force.

optoPAK1 is a genetically encoded, light-responsive optogenetic analog of p21-activated kinase 1 (PAK1) engineered for photoinduced recruitment to specified intracellular sites. It was designed as a constitutively active PAK1 variant that functions independently of endogenous biochemical regulation while maintaining minimal dark-state activity.

optoRAF is an optogenetic multi-component switch for light-controlled clustering and activation of RAF proteins. It was described as mimicking naturally occurring RAS-mediated RAF dimerization and was used to probe BRAF and CRAF responses to kinase inhibitors.

PA-Cre 3.0 is a genetically encoded photoactivatable Cre recombinase system for light-controlled recombination in mammalian cells and in vivo mouse applications. It is an updated multi-component switch engineered to reduce background recombination and improve blue-light-induced Cre activity.

PA-Cre2.0 is a photoactivatable split Cre recombinase in which Cre activity is reconstituted by light-induced CRY2-CIB1 dimerization. It enables light-dependent control of Cre-mediated recombination and has been functionally characterized in mammalian cells and rodent brain.

The photo-activatable Akt probe (PA-Akt) is a light-controlled multi-component Akt activation system built from the plant CRY2-CIB1 light-inducible interaction module. Upon illumination, it activates Akt signaling with sequential phosphorylation of Akt at S473 and T308 and engages downstream GSK-3β signaling in a light-intensity-dependent manner.

Photoactivatable Cre recombinase is a light-controlled recombination tool reported in a 2016 Nature Chemical Biology study. The available evidence links it to optimized second-generation CRY2–CIB dimerizers and indicates that it enables light regulation of Cre-mediated recombination.

PhyB-CreC is the PhyB-fused C-terminal half of Cre recombinase in the CreLite optogenetic split-Cre system. In the presence of phycocyanobilin and 660 nm red light, it associates with PIF6-CreN to reconstitute Cre activity and drive Cre/loxP-dependent recombination in zebrafish embryos.

phyB/PIF6 is a red-light-regulated optical dimerizer system composed of phyB and PIF6. In a yeast transcriptional assay, it supported light-dependent regulation and was benchmarked against phyB/PIF3, CRY2/CIB1, and TULIPs, with significant differences reported between phyB/PIF6 and phyB/PIF3 in light sensitivity and fold activation.

PIF6-CreN is the PIF6-fused N-terminal Cre fragment used in the CreLite optogenetic recombinase system. In the presence of phycocyanobilin (PCB), 660 nm red light induces association with PhyB-CreC, reconstituting Cre recombinase activity for light-controlled loxP recombination in developing zebrafish embryos.

Single-component optogenetic tools were created to control RhoA GTPase signaling with light. The reported system does not require protein binding partners and enables inducible RhoA-mediated cytoskeletal activation with downstream YAP nuclear localization and YAP-TEAD mechanotranscription.

The split synthetic zinc-finger transcription factor is a light-controlled transcriptional switch developed for Saccharomyces cerevisiae. Its activity is reconstituted from split components through CRY2- and CIB1-mediated light-induced dimerization, enabling optical control of gene expression.

The SspB A58V iLID dimer variant is a blue-light-inducible, multi-component protein interaction system in which a single A58V substitution in SspB tunes binding to iLID. It mediates light-gated heterodimerization and was reported to enable light-activated colocalization of transmembrane proteins in neurons.

tdnano is a constructed tandem-dimer of the iLID binding partner nano used as the second component of a blue-light-responsive iLID system. In the reported opto-receptor tyrosine kinase designs, blue light drives recruitment of two iLID-fused RTK molecules to tdnano, enabling receptor dimerization and activation.

This tool is a two-photon-sensitive chemical caging group applied to gibberellic acid 3 (GA3) to permit infrared-light-triggered release of active GA3 in living cells. The uncaged GA3 is used to induce protein dimerization.

WCC, the white collar complex, is a light-responsive heterodimeric complex in Neurospora composed of the PAS-domain-containing proteins WC-1 and WC-2. The available evidence identifies it as a major photoreceptor and suggests a role in transcriptional regulation through zinc-finger-containing subunits.

synPCB is a genetically encoded phycocyanobilin synthesis system that supplies the chromophore required for PhyB-PIF phytochrome-based optogenetics. The improved synPCB version increased PCB production by approximately 4-fold and was incorporated with PhyB-PIF into doxycycline-inducible lentiviral and transposon vectors to support light-inducible dimerization system expression or function.

a real-time dynamic hologram of a realistic 3D object based on fast photochromic imidazole dimers

The cryptochrome 2-mediated optogenetic C-RAF activation tool is a mammalian-cell optogenetic system in which Arabidopsis thaliana cryptochrome 2 drives blue light-dependent dimerization to activate the protein kinase C-RAF. It enables reversible optical control of C-RAF signaling outputs, including ERK1/2 phosphorylation and serum response factor-mediated gene expression.

Light-activated neurotrophin receptors are engineered optogenetic multi-component receptor systems built using the improved light-induced dimerizer (iLID). The available evidence indicates that they use light-controlled iLID interactions to drive neurotrophin receptor assembly or activation.

Optical dimerizers are genetically encoded actuators that use light to control protein-protein interactions. The cited examples are the CRY2/CIB and UVR8/UVR8 systems, which have been applied to light-regulated transcription, protein localization, and protein secretion.

Opto-kinases are a growing set of optogenetic multi-component tools that use light to activate or inhibit different protein kinases. They are described as tools for regulating cellular signaling with temporal and spatial control.

UVR8 is an Arabidopsis thaliana UV-B photoreceptor that senses solar UV-B light in the 280-315 nm range. It functions as a light-responsive multi-component switch through UV-B-induced dissociation of a UVR8 dimer.

UVR8/UVR8 is a light-controlled protein interaction system described as one of two optical dimerizer platforms in a protocol-focused study. It is presented for regulating cellular processes including transcription, protein localization, and protein secretion using light.

The blue light-inducible cryptochrome-based dimerization system is a light-responsive multi-component switch that uses blue light to induce protein dimerization. The cited evidence supports its use for spatiotemporally precise control of signaling or cytoskeletal events.

The blue light-inducible LOV domain-based dimerization system is a light-responsive multi-component switch in which blue light induces dimerization to control intracellular signaling or cytoskeletal events. The cited literature describes this class of systems as providing spatiotemporally precise perturbation of cell behavior.

eGAV (enhanced Gal4-VVD transcription factor) is a light-controlled transcription switch for mammalian and vertebrate systems. It mediates inducible gene expression and has been validated in cultured HEK293T and mouse EpH4 cells, as well as in mouse brain, chick spinal cord, and adult mouse hepatocytes.

The light-activatable gp41-1 intein is an engineered split intein system that enables blue light–dependent protein splicing to control Cre recombinase activity in mammalian cells. It is a multi-component switch derived from gp41-1 split variants engineered at unnatural split sites with reduced fragment affinity, allowing conditional reconstitution of Cre.

The light-activatable NrdJ-1 intein is a blue-light-gated split intein system engineered for regulated protein splicing in mammalian cells. In the reported study, it enabled blue light–dependent reconstitution of Cre recombinase activity and was used to drive recombination-linked outputs, including spatial control of apoptosis.

The near-infrared light activatable chemically induced split-Cas9/dCas9 system is a multi-component CRISPR switch in which split Cas9 or dCas9 is activated through a near-infrared photocleavable dimerization complex. It is intended to provide near-infrared light-gated control of CRISPR genome editing-related activity.

The NIR light-activated CRISPR-dCas9/Cas9 system is a multi-component optogenetic platform that controls CRISPR-dCas9/Cas9 gene regulation and editing with near-infrared light. It uses a chemically cleavable rapamycin dimer to confer precise and rapid light-dependent activity in living organisms.

Single-construct optogenetic talin is an engineered light-responsive talin system in which pdDronpa1.2 enables light-inducible C-terminal talin homodimerization. In the cited study, this induced talin recruitment to adhesion sites, promoted adhesion formation, engaged actin retrograde flow, and activated downstream mechanosignaling.

UNICYCL is a red-light-regulated multi-component protein interaction switch built from the cyanobacteriochrome NpF2164g6 and the binder BNp-Red-1.2. In the dark, BNp-Red-1.2 forms a 1:1 complex with NpF2164g6 with an approximately 1–5 μM dissociation constant, enabling reversible light-controlled association.

LITEs (Light-inducible transcriptional effectors) are a light-controlled, multi-component transcriptional regulation system assembled from two modular components. In the cited study, an optogenetic CRISPR-dCas9 LITE system was used to manipulate endogenous PIM1 transcription in U87 glioblastoma cells in vitro.

The genetically encoded PhyB–PIF light-inducible dimerization system is an optogenetic multi-component switch that uses a PhyB-based light-induced dimerization interaction to control signal transduction. The cited chapter describes a genetically encoded implementation enabled by efficient phycocyanobilin synthesis in cultured mammalian cells and reports applications in cultured cells and animals.

Cry2-Cib is a light-responsive photodimerizing protein pair used as a multi-component optogenetic switch. In the cited application, light stimulation drives translocation of a low-constitutive-activity protein kinase A catalytic subunit to a subcellular region containing Cib, thereby restoring kinase activity.

phyB/PIF3 is a red-light-regulated multi-component optical dimerizer system benchmarked in a yeast transcriptional assay. It uses light-controlled heterodimerization between phyB and PIF3 to regulate transcriptional output.

The anchor-away (AA) technique enables rapid depletion of nuclear proteins by tethering them to cytoplasmic anchors through rapamycin-induced heterodimerisation.

resulting in various coiled-coil heterodimers-mediated base editors (CC-BEs), including ... adenine base editor (CC-ABE)... Using CC-ABE, we validate in vivo editing efficiency and successfully achieve A-to-G conversion in the Pcsk9 and Dmd genes via dual-AAV vectors in mice.

resulting in various coiled-coil heterodimers-mediated base editors (CC-BEs), including cytidine base editor (CC-CBE)... achieving maximum enhancements of 9.6-fold in human immortalized cells and 12.4-fold in primary somatic cells for CC-CBE.

Here we design a split BE system that recruits deaminases to Cas9 nickase via coiled-coil heterodimers, resulting in various coiled-coil heterodimers-mediated base editors (CC-BEs).

The SNACIP inducer cRGT carrying a cyclic cell-penetrating peptide rapidly enters live cells and dimerizes eDHFR and GFP-variants.

Here, we generate monomeric bacteriophytochrome PSMs that form stable heterodimers once mixed by modifying two salt bridges at the dimerization interface of the Deinococcus radiodurans phytochrome (DrBphP).

The vault cap features a positively charged exterior and a negatively charged interior surface, with implications for binding partner recruitment and engineering of modified vault particles.

Using this new BRET system, we also designed a mTOR pathway specific rapamycin biosensor by integrating the FRB and FKBP12 protein dimerization system.

Optogenetic PLDs use light-mediated heterodimerization to recruit a bacterial PLD to desired organelle membranes

Here, we demonstrate a strategy termed 'P3 editing', which links protein-protein proximity to the formation of a functional CRISPR-Cas9 dual-component guide RNA.

The supplied web research summary states that the review spans photoactivatable genome editing and that the directly matching primary paper identifies the split Cas9 light-inducible system as paCas9 using pMag and nMag.

PhoBIT1, a light-OFF switch generated by integrating LOV2 into sspB

PhoBIT2, a light-ON switch building upon an evolved ssrA/CRY2-sspB pair with minimal basal interaction

Here, we report the design of a protease-responsive conformationally inhibited system (PRCIS). By intramolecularly linking the free DNA-binding domains of ATF to confined dimerized regions, the transcriptional binding is conformationally inactivated. The function of DNA binding is reinstated upon proteolytic cleavage of linkages, activating the downstream gene expressions.

Here, we review recent advancements to modulate Cas9-mediated genome editing by engineering... protein-based dimerizing domains...

here we employed a rapamycin-inducible FKBP-FRB dimerization system to artificially tether CAP-D2 and SMC4 either between different complexes (inter-complex tethering) or within single complexes (intra-complex tethering)

Here, we develop red/far-red light-regulated individually encapsulated (RL/FRL-EnE) cells, integrating optogenetics with biomaterial encapsulation for precise immunomodulation.

This system uses a phytochrome A-based photoswitch (ΔPhyA-PCB) that enables bidirectional control.

As a tool component, CIB1 is most directly supported as the cryptochrome-interacting bHLH partner used with CRY2 to create blue-light-controlled protein association systems. In these systems, CIB1 is typically fused to localization, transcriptional, or enzymatic modules so that blue light drives CRY2–CIB1 binding and light withdrawal reverses the interaction.

SspB is the binding partner used in the iLID blue-light-inducible dimerization system. Upon blue-light activation of iLID, the exposed SsrA peptide binds SspB, enabling light-controlled recruitment and localization of SspB-fused cargo proteins.

The Light-Oxygen-Voltage (LOV) domain is a small blue-light-sensing protein domain used as an optogenetic input module. It binds flavin nucleotides and undergoes blue-light-induced structural rearrangements that can regulate linked effector domains, including in phototropins where LOV1 and LOV2 are coupled to a C-terminal serine/threonine kinase.

nano is the wild-type SspB protein used as the binding partner for iLID in a blue-light-responsive dimerization system. In the cited work, the iLID–nano pair is used to control protein interactions and localization with light.

PpSB1-LOV is a bacterial short LOV photosensory domain from Pseudomonas putida KT2440 with a light-induced flavin-cysteinyl photo-adduct and exceptionally slow dark recovery. It has been characterized as a compact LOV building block whose photocycle kinetics can be tuned by conserved hydrophobic-pocket mutation, including the I48T variant that accelerates adduct rupture while remaining structurally and mechanistically benign.

YtvA is a blue-light-sensing LOV-STAS photoreceptor from Bacillus subtilis whose LOV domain has been structurally analyzed for LOV-LOV dimerization and interdomain interactions. Homologous mutations in a conserved LOV hydrophobic pocket alter activation-state kinetics, supporting YtvA as a tunable LOV sensor domain relevant to optogenetic design.

split-TurboID is a split proximity-labeling enzyme used in the Light Activated BioID (LAB) system, where its two halves are fused to the photodimeric proteins CRY2 and CIB1. Blue light induces CRY2–CIB1 association, reconstitutes split-TurboID, and triggers proximity-dependent biotinylation.

Enhanced Magnets (eMags) are Vivid-derived light-sensitive protein dimerization domains used in optogenetic split transcription factors and subcellular recruitment systems. In Saccharomyces cerevisiae, optimized eMag-based transcription factor designs improved light-sensitive gene expression, and eMags were also validated for rapid, reversible protein recruitment to subcellular organelles.

The Avena sativa LOV2 domain is a blue-light-sensing photosensory domain used as a photoswitchable scaffold for engineered control of protein interactions. In the iLID design, the bacterial SsrA peptide is embedded in the LOV2 C-terminal helix so that blue light triggers helix undocking and enables binding to SspB.

The Arabidopsis thaliana phototropin 1 LOV2 domain is a blue-light-sensing protein domain from phototropin 1 whose dark-adapted crystal structure has been determined. In this state, the domain is dimeric and contains an N-terminal A'α helix and a C-terminal Jα helix that contribute to coiled-coil-mediated dimerization.

PpSB2-LOV is a compact "short" light, oxygen, voltage (LOV) photosensory protein from Pseudomonas putida KT2440. It forms a light-induced LOV photoadduct and exhibits rapid dark-state thermal recovery, with a reported recovery time of 3.5 min at 20 °C, making it a candidate building block for genetically encoded photoswitches.

TAEL is an engineered optogenetic transcription factor optimized for zebrafish in which blue light induces TAEL dimerization, binding to the C120 promoter element, and activation of downstream transcription. TAEL 2.0 is an improved transgenic implementation that enables inducible expression at late embryonic and larval stages and produces faster, higher reporter expression than the original system.

Cryptochromes are blue/ultraviolet-A light-responsive photoreceptor protein domains, including Arabidopsis thaliana cry1 and cry2 variants, that were incorporated into a yeast optogenetic toolkit. In this toolkit context, cryptochrome variants were used as light-sensitive modules in split transcription factors to optically control transcription.

Arabidopsis thaliana cryptochrome 2 (CRY2) is a plant photoreceptor protein domain used as an optogenetic module. In the supplied evidence, CRY2 mediates blue light-dependent dimerization to activate C-RAF in mammalian cells.

The Aer PAS domain is the FAD-binding sensory domain from the dimeric Escherichia coli aerotaxis receptor Aer. It monitors cellular respiration through a redox-sensitive flavin cofactor and is structurally characterized in the Aer-PAS-GVV variant at 2.4 Å resolution.

The Drosophila PERIOD PAS domain fragment is a dPER protein segment comprising the PAS-A and PAS-B domains. Structural and functional analyses indicate that this fragment participates in PAS-mediated protein interactions, with the PAS-B beta-sheet surface mediating heterodimer formation with Drosophila TIMELESS (dTIM).

The Drosophila PERIOD PAS-B beta-sheet surface is a protein interaction interface within dPER that mediates binding to the clock protein TIMELESS (dTIM). Comparative analysis further indicates that this PAS-B beta-sheet surface is a reusable interaction site within PERIOD-family proteins, supporting dPER-dTIM heterodimer formation in Drosophila and mPER2 homodimerization in mammals.

GntR is a gluconate-responsive transcriptional repressor from Escherichia coli that has been repurposed as a protein domain for synthetic gene-control switches. Reported designs use GntR to construct gluconate-regulated transcriptional systems in mammalian cells, including rewired OFF/ON transcriptional architectures and a split transcriptional activator.

The heme PAS domain of Escherichia coli direct oxygen sensor (Ec DOS) is a bacterial heme-binding sensor domain structurally characterized in inactive Fe(3+) and active Fe(2+) states. It acts as a redox-responsive molecular switch in which changes in heme coordination are coupled to conformational rearrangements within the PAS domain.

The integrin αIIb cytoplasmic domain is a platelet integrin tail segment that functions as a specific binding partner for the calcium- and integrin-binding protein CIB1. Solution structural analysis indicates that this interaction involves EF-hand III of CIB1 and is associated with a CIB1 conformational response distinct from that of related EF-hand proteins.

Q-PAS1 is an engineered single-domain binding partner for the bacterial phytochrome BphP1 that enables near-infrared-light-inducible protein interactions. It was developed as a smaller, non-oligomerizing alternative to the natural BphP1 partner PpsR2 and has been applied to transcription regulation, chromatin state modification, and spectral multiplexing.

The RhoPDE C-terminal phosphodiesterase catalytic domain is the isolated catalytic region of the rhodopsin/phosphodiesterase fusion protein RhoPDE from the choanoflagellate Salpingoeca rosetta. It has been expressed, purified, and structurally characterized by crystallography, while the parent full-length protein was reported to function as a cGMP-selective phosphodiesterase.

The SMN tudor domain is a globular protein domain from SMN that is sufficient for dimerization-induced condensation in vivo. Its condensate-forming activity requires binding to dimethylarginine, supporting its use as a chemical-input interaction module for specifying membraneless organelle assembly.

The TRIM21 RING domain is a catalytic protein domain whose ubiquitination activity is activated by substrate-induced clustering that promotes intermolecular RING dimerization. In the cited 2020 study, this activation mechanism underlies TRIM21-dependent antiviral responses and Trim-Away-mediated protein degradation.

The basic helix-loop-helix (bHLH) domain is a highly conserved eukaryotic protein motif present in transcription factors. It contains a basic DNA-binding region and a helix-loop-helix region, supporting transcriptional regulatory functions across diverse physiological contexts.

The aureochrome 1 LOV-domain-based optical TrkB activation approach is an optogenetic TrkB activation strategy built around the light-oxygen-voltage domain of aureochrome 1 from Vaucheria frigida. It was presented as a demonstration that optical TrkB activation can be implemented with an optical homo-dimerizer other than CRY2.

Cyanobacteriochromes are photoswitchable protein domains from cyanobacteria that sense light across a broad spectral range from the UV to the near infra-red. In the cited 2022 work, they were engineered into light-inducible dimer pairs that support orthogonal control with red, green, and blue light.

EL346 is a full-length blue light-activated histidine kinase from Erythrobacter litoralis HTCC2594 that contains a LOV photosensor domain. Structural evidence indicates that the LOV domain regulates kinase state by controlling intramolecular domain interactions, maintaining an inhibited dark-state conformation, and releasing that inhibition upon photoactivation.

The ITSN1 GEF domain is a guanine-nucleotide exchange factor domain from ITSN1 that has been incorporated into Opto-RhoGEF constructs for light-controlled regulation of Rho GTPase signaling. In the cited 2023 eLife study, constructs containing GEF domains from ITSN1 supported reversible optogenetic control of endothelial cell morphology and vascular barrier strength.

The light-oxygen-voltage (LOV) sensor domain is a light-responsive regulatory protein domain characterized in the monomeric histidine kinase EL346. Structural evidence indicates that it binds one side of the DHpL domain to control kinase output, prevent dimerization, and release the catalytic apparatus from an inhibited conformation upon photoactivation.

Optogenetic RGS2 (opto-RGS2) is an engineered light-responsive RGS2-based protein tool created to study calcium encoding in Gq-protein signaling. It uses light-induced heterodimerization to recruit an RGS2 domain to the membrane, where it interacts with its cognate G protein and modulates calcium oscillatory behavior.

The p63RhoGEF GEF domain is a guanine-nucleotide exchange factor domain incorporated into Opto-RhoGEF constructs for light-controlled regulation of Rho GTPase signaling. In the cited 2023 eLife study, Opto-RhoGEFs using GEF domains including p63RhoGEF enabled reversible control of endothelial cell morphology and vascular endothelial barrier strength.

The TIAM1 GEF domain is a guanine-nucleotide exchange factor domain used as a modular component in Opto-RhoGEF systems. In the cited 2023 eLife study, Opto-RhoGEFs provided reversible light-responsive control of Rho GTPase-dependent endothelial morphology and vascular barrier strength.

YtvA from Bacillus subtilis is a LOV-domain photoswitch reported in this evidence set as a homodimeric light-responsive protein domain. It was highlighted in an optogenetics context because its relaxation half-life is longer than that of Avena sativa LOV2, suggesting potential utility as a light-controlled module.

Vivid (VVD) is a blue-light-sensing light-oxygen-voltage (LOV) protein from the filamentous fungus Neurospora crassa. Upon illumination, its flavin cofactor forms a photoadduct that creates a stable light state, while VVD also exhibits light-dependent dimer-associated aggregation behavior and photosensitized self-oxidation.

The Rel/NF-κB family is a mammalian set of transcription factors comprising RelA, c-Rel, RelB, NF-κB1 (p50 and precursor p105), and NF-κB2 (p52 and precursor p100). These factors are differentially activated as NF-κB heterodimers by signals from antigen receptors, pattern-recognition receptors, and receptors for TNF and IL-1 family cytokines to regulate transcription.

pdDronpa1.2 is a protein domain used in a single-construct optogenetic talin system to enable light-inducible C-terminal homodimerization. In the cited 2025 study, this light-triggered talin dimerization was sufficient to drive talin recruitment to adhesion sites, adhesion formation, coupling to actin retrograde flow, and downstream mechanosignaling.

The dimerization/histidine phosphotransfer-like (DHpL) domain is a regulatory domain element within the blue-light-responsive histidine kinase EL346. Structural evidence indicates that, in the dark, interactions involving the LOV sensor domain and the DHpL domain stabilize an inhibited kinase conformation and suppress dimerization, while photoactivation weakens these contacts to promote activation.

The nMag/pMag photodimerization system, also called Magnets photosensors, is a light-controlled protein-domain pair that mediates heterodimerization. Reported engineering work altered its light sensitivity and tuned its light-activity dose-response behavior through directed evolution and high-throughput screening.

The AUREO1 LOV-only construct is an isolated LOV photosensory domain derived from aureochrome-1. In the cited study, blue light induced a secondary-structure shift from increased alpha-helical to increased beta-sheet character in this LOV-only construct without a detectable change in hydrodynamic radius.

The light-oxygen-voltage sensing (LOV) domain is a blue light-responsive protein domain used in optogenetic constructs to confer light-dependent control over coupled signaling effectors. The supplied evidence specifically describes it as a blue light homodimerizing LOV domain.

The Rhodobacter sphaeroides light-oxygen-voltage domain (RsLOV) is a homodimeric LOV photosensory protein domain from Rhodobacter sphaeroides. Reported engineering results indicate that fusion of RsLOV to Cas9-derived effector variants can confer light sensitivity, and the same domain also imparted strong temperature sensitivity in that study.

The CIB1 N-terminal CRY2-binding region is a protein domain derived from the N terminus of calcium and integrin-binding protein 1 (CIB1). It serves as the CIB1 partner in blue light-activated CRY2-CIB1 optogenetic dimerization systems.

The supplied web research summary states that PubMed figure captions for the anchor review explicitly name nMag as the partner to pMag for split Cas9 reconstitution.

The supplied web research summary identifies pdDronpa as a photodissociable dimeric Dronpa component used to cage and uncage protein activity in photoswitchable kinases.

The supplied web research summary states that PubMed figure captions for the anchor review explicitly name pMag as one half of the light-induced dimerization pair used to reconstitute split Cas9.