Source 1primary paper2019ACS Synthetic Biology
Toolkit/cLIPS1
cLIPS1
Also known as: circularly permuted LOV inhibitor of protein synthesis 1
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
cLIPS1 is a photoactivated translation inhibitor built by fusing a segment of 4EBP2 to a circularly permuted Avena sativa LOV2 domain. It binds human eIF4E in a light-dependent manner and inhibits translation in a yeast system engineered to harbor human eIF4E.
Usefulness & Problems
Why this is useful
cLIPS1 provides an optogenetic means to control translation initiation with light through regulated interaction with human eIF4E. It is useful as a tool for perturbing the translation machinery in a temporally controlled manner in the reported yeast-based context.
Source:
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
Source:
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
Problem solved
cLIPS1 addresses the problem of achieving light-dependent inhibition of eukaryotic translation initiation. Specifically, it enables photoactivated targeting of human eIF4E to suppress translation in vivo in yeast harboring human eIF4E.
Problem links
Need precise spatiotemporal control with light input
DerivedcLIPS1 is a photoactivated translation inhibitor built by fusing a segment of 4EBP2 to a circularly permuted Avena sativa LOV2 domain. It binds human eIF4E in a light-dependent manner and inhibits translation in a yeast system engineered to harbor human eIF4E.
Need tighter control over protein production
DerivedcLIPS1 is a photoactivated translation inhibitor built by fusing a segment of 4EBP2 to a circularly permuted Avena sativa LOV2 domain. It binds human eIF4E in a light-dependent manner and inhibits translation in a yeast system engineered to harbor human eIF4E.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Mechanisms
light-dependent protein-protein bindingtranslation controlTranslation Controltranslation initiation inhibitionTechniques
No technique tags yet.
Target processes
translationInput: 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: regulatorswitch architecture: multi component
cLIPS1 is a fusion construct comprising a segment of 4EBP2 and a circularly permuted LOV2 domain from Avena sativa. Reported functional validation was performed using human eIF4E and a yeast system engineered to harbor human eIF4E; the supplied evidence does not provide additional construct architecture or expression details.
The supplied evidence is limited to a single 2019 study and to in vitro binding plus in vivo activity in a yeast system harboring human eIF4E. No quantitative performance metrics, wavelength details, reversibility data, or validation in mammalian cells are provided in the supplied evidence.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Observations
successYeastapplication demo
Inferred from claim c4 during normalization. cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo. Derived from claim c4. Quoted text: We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
Source:
successYeastapplication demo
Inferred from claim c4 during normalization. cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo. Derived from claim c4. Quoted text: We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
Source:
successYeastapplication demo
Inferred from claim c4 during normalization. cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo. Derived from claim c4. Quoted text: We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
Source:
successYeastapplication demo
Inferred from claim c4 during normalization. cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo. Derived from claim c4. Quoted text: We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
Source:
successYeastapplication demo
Inferred from claim c4 during normalization. cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo. Derived from claim c4. Quoted text: We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
Source:
successYeastapplication demo
Inferred from claim c4 during normalization. cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo. Derived from claim c4. Quoted text: We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
Source:
successYeastapplication demo
Inferred from claim c4 during normalization. cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo. Derived from claim c4. Quoted text: We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
Source:
Supporting Sources
Ranked Claims
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 is a photoactivated inhibitor of translation.
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
cLIPS1 is a photoactivated inhibitor of translation.
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
cLIPS1 is a photoactivated inhibitor of translation.
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
cLIPS1 is a photoactivated inhibitor of translation.
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
cLIPS1 is a photoactivated inhibitor of translation.
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
cLIPS1 is a photoactivated inhibitor of translation.
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
cLIPS1 is a photoactivated inhibitor of translation.
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
Approval Evidence
1 source3 linked approval claimsfirst-pass slug clips1
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
Source:
binding activitysupports
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
Source:
functional activitysupports
cLIPS1 is a photoactivated inhibitor of translation.
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
Source:
in vivo activitysupports
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
Source:
Comparisons
Source-backed strengths
The tool was reported to bind human eIF4E in vitro in a light-dependent manner and to inhibit translation in vivo in yeast harboring human eIF4E. Its design links a defined translation regulatory segment from 4EBP2 to a photosensory LOV2 module, supporting direct optical control of a translation-initiation interaction.
Source:
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
Compared with LiGluR-MAG0(460)
cLIPS1 and LiGluR-MAG0(460) address a similar problem space because they share translation.
Shared frame: same top-level item type; shared target processes: translation; shared mechanisms: translation_control; same primary input modality: light
Strengths here: looks easier to implement in practice; may avoid an exogenous cofactor requirement.
Compared with optogenetic systems adapted to regulate gene expression
cLIPS1 and optogenetic systems adapted to regulate gene expression address a similar problem space because they share translation.
Shared frame: same top-level item type; shared target processes: translation; shared mechanisms: translation control, translation_control; same primary input modality: light
Compared with prime-editing
cLIPS1 and prime-editing address a similar problem space because they share translation.
Shared frame: same top-level item type; shared target processes: translation; shared mechanisms: translation_control; same primary input modality: light
Strengths here: may avoid an exogenous cofactor requirement.
Relative tradeoffs: appears more independently replicated.
Ranked Citations
- 1.