Source 1primary paper2015ChemBioChem
Toolkit/hybrid phototropin LOV2 domains incorporating the BID BH3 region
hybrid phototropin LOV2 domains incorporating the BID BH3 region
Also known as: designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of BID, light-dependent optogenetic tool
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Hybrid phototropin LOV2 domains were engineered to incorporate the BID Bcl homology region 3 (BH3), creating a light-dependent optogenetic switch. Illumination induces LOV2 conformational changes that expose the BH3 element and modulate binding to the anti-apoptotic Bcl-2 family protein Bcl-xL.
Usefulness & Problems
Why this is useful
This tool provides optical control over a specific protein-protein interaction involving the BID BH3 motif and Bcl-xL. It is useful for studying and perturbing Bcl-2 family interactions with light-dependent temporal control.
Source:
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
Problem solved
It addresses the problem of conditionally exposing a pro-apoptotic BH3 peptide sequence so that interaction with Bcl-xL can be regulated by light rather than remaining constitutively available. The evidence supports modulation of Bcl-xL binding, but does not establish broader functional outputs beyond this interaction.
Problem links
Need conditional recombination or state switching
DerivedHybrid phototropin LOV2 domains were designed to incorporate the BID Bcl homology region 3 (BH3), creating a light-dependent optogenetic switch. Upon illumination, conformational changes in the LOV2-associated amphiphilic alpha-helix expose the BH3 element and modulate binding to the anti-apoptotic Bcl-2 family protein Bcl-xL.
Need precise spatiotemporal control with light input
DerivedHybrid phototropin LOV2 domains were designed to incorporate the BID Bcl homology region 3 (BH3), creating a light-dependent optogenetic switch. Upon illumination, conformational changes in the LOV2-associated amphiphilic alpha-helix expose the BH3 element and modulate binding to the anti-apoptotic Bcl-2 family protein Bcl-xL.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Mechanisms
conformational uncagingconformational uncagingConformational Uncagingcovalent cysteinyl-flavin adduct formationcovalent cysteinyl-flavin adduct formationlight-dependent modulation of protein-protein interactionlight-dependent modulation of protein-protein interactionTechniques
Computational DesignTarget processes
recombinationInput: Light
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: multi component delivery burdenimplementation constraint: spectral hardware requirementoperating role: actuatoroperating role: regulatorswitch architecture: multi componentswitch architecture: uncaging
The construct is a hybrid domain fusion in which the BID BH3 region is incorporated into a phototropin LOV2 scaffold. Its photoswitching mechanism depends on covalent cysteinyl-flavin adduct formation and signal propagation through hydrogen-bonding networks in the LOV2 protein core.
The available evidence is limited to a single cited study and focuses on mechanism and interaction modulation with Bcl-xL. The provided evidence does not report independent replication, quantitative performance metrics, wavelength details, or validation across multiple biological contexts.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
Approval Evidence
1 source2 linked approval claimsfirst-pass slug hybrid-phototropin-lov2-domains-incorporating-the-bid-bh3-region
designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID)
Source:
functionsupports
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
Source:
mechanismsupports
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
Source:
Comparisons
Source-backed strengths
The design couples a defined LOV2 photosensory conformational response to exposure of an embedded BH3 sequence. Source claims indicate that light-dependent modulation of Bcl-xL interaction is achieved through the flanking amphiphilic alpha-helix and LOV2 core signaling pathway.
Compared with engineered focal adhesion kinase two-input gate
hybrid phototropin LOV2 domains incorporating the BID BH3 region and engineered focal adhesion kinase two-input gate address a similar problem space because they share recombination.
Shared frame: same top-level item type; shared target processes: recombination; shared mechanisms: conformational uncaging, conformational_uncaging; same primary input modality: light
Compared with iLID/SspB
hybrid phototropin LOV2 domains incorporating the BID BH3 region and iLID/SspB address a similar problem space because they share recombination.
Shared frame: same top-level item type; shared target processes: recombination; shared mechanisms: conformational uncaging, conformational_uncaging; same primary input modality: light
Relative tradeoffs: appears more independently replicated; looks easier to implement in practice.
Compared with LOV2-based photoswitches
hybrid phototropin LOV2 domains incorporating the BID BH3 region and LOV2-based photoswitches address a similar problem space because they share recombination.
Shared frame: same top-level item type; shared target processes: recombination; shared mechanisms: conformational uncaging, conformational_uncaging; same primary input modality: light
Relative tradeoffs: appears more independently replicated; looks easier to implement in practice.
Ranked Citations
- 1.