Toolkit/cLIPS1

cLIPS1

Multi-Component Switch·Research·Since 2019

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

Derived

cLIPS1 is a photoactivated inhibitor of translation composed of a 4EBP2 segment fused to a circularly permuted Avena sativa LOV2 domain. It binds human eIF4E in a light-dependent manner and inhibits translation in a yeast system harboring human eIF4E.

Need tighter control over protein production

Derived

cLIPS1 is a photoactivated inhibitor of translation composed of a 4EBP2 segment fused to a circularly permuted Avena sativa LOV2 domain. It binds human eIF4E in a light-dependent manner and inhibits translation in a yeast system harboring human eIF4E.

Taxonomy & Function

Primary hierarchy

Mechanism Branch

Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.

Techniques

No technique tags yet.

Target processes

translation

Input: 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

Claim 1binding activitysupports2019Source 1needs review

cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.

and bind human eIF4E in vitro in a light-dependent manner.
Claim 2binding activitysupports2019Source 1needs review

cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.

and bind human eIF4E in vitro in a light-dependent manner.
Claim 3binding activitysupports2019Source 1needs review

cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.

and bind human eIF4E in vitro in a light-dependent manner.
Claim 4binding activitysupports2019Source 1needs review

cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.

and bind human eIF4E in vitro in a light-dependent manner.
Claim 5binding activitysupports2019Source 1needs review

cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.

and bind human eIF4E in vitro in a light-dependent manner.
Claim 6binding activitysupports2019Source 1needs review

cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.

and bind human eIF4E in vitro in a light-dependent manner.
Claim 7binding activitysupports2019Source 1needs review

cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.

and bind human eIF4E in vitro in a light-dependent manner.
Claim 8binding activitysupports2019Source 1needs review

cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.

and bind human eIF4E in vitro in a light-dependent manner.
Claim 9binding activitysupports2019Source 1needs review

cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.

and bind human eIF4E in vitro in a light-dependent manner.
Claim 10binding activitysupports2019Source 1needs review

cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.

and bind human eIF4E in vitro in a light-dependent manner.
Claim 11binding activitysupports2019Source 1needs review

cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.

and bind human eIF4E in vitro in a light-dependent manner.
Claim 12binding activitysupports2019Source 1needs review

cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.

and bind human eIF4E in vitro in a light-dependent manner.
Claim 13binding activitysupports2019Source 1needs review

cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.

and bind human eIF4E in vitro in a light-dependent manner.
Claim 14binding activitysupports2019Source 1needs review

cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.

and bind human eIF4E in vitro in a light-dependent manner.
Claim 15binding activitysupports2019Source 1needs review

cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.

and bind human eIF4E in vitro in a light-dependent manner.
Claim 16binding activitysupports2019Source 1needs review

cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.

and bind human eIF4E in vitro in a light-dependent manner.
Claim 17binding activitysupports2019Source 1needs review

cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.

and bind human eIF4E in vitro in a light-dependent manner.
Claim 18functional activitysupports2019Source 1needs review

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.
Claim 19functional activitysupports2019Source 1needs review

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.
Claim 20functional activitysupports2019Source 1needs review

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.
Claim 21functional activitysupports2019Source 1needs review

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.
Claim 22functional activitysupports2019Source 1needs review

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.
Claim 23functional activitysupports2019Source 1needs review

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.
Claim 24functional activitysupports2019Source 1needs review

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.
Claim 25functional activitysupports2019Source 1needs review

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.
Claim 26functional activitysupports2019Source 1needs review

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.
Claim 27functional activitysupports2019Source 1needs review

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.
Claim 28functional activitysupports2019Source 1needs review

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.
Claim 29functional activitysupports2019Source 1needs review

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.
Claim 30functional activitysupports2019Source 1needs review

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.
Claim 31functional activitysupports2019Source 1needs review

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.
Claim 32functional activitysupports2019Source 1needs review

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.
Claim 33functional activitysupports2019Source 1needs review

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.
Claim 34functional activitysupports2019Source 1needs review

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.
Claim 35in vivo activitysupports2019Source 1needs review

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
Claim 36in vivo activitysupports2019Source 1needs review

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
Claim 37in vivo activitysupports2019Source 1needs review

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
Claim 38in vivo activitysupports2019Source 1needs review

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
Claim 39in vivo activitysupports2019Source 1needs review

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
Claim 40in vivo activitysupports2019Source 1needs review

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
Claim 41in vivo activitysupports2019Source 1needs review

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
Claim 42in vivo activitysupports2019Source 1needs review

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
Claim 43in vivo activitysupports2019Source 1needs review

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
Claim 44in vivo activitysupports2019Source 1needs review

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
Claim 45in vivo activitysupports2019Source 1needs review

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
Claim 46in vivo activitysupports2019Source 1needs review

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
Claim 47in vivo activitysupports2019Source 1needs review

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
Claim 48in vivo activitysupports2019Source 1needs review

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
Claim 49in vivo activitysupports2019Source 1needs review

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
Claim 50in vivo activitysupports2019Source 1needs review

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
Claim 51in vivo activitysupports2019Source 1needs review

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
Claim 52optimization outcomesupports2019Source 1needs review

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.
Claim 53optimization outcomesupports2019Source 1needs review

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.
Claim 54optimization outcomesupports2019Source 1needs review

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.
Claim 55optimization outcomesupports2019Source 1needs review

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.
Claim 56optimization outcomesupports2019Source 1needs review

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.
Claim 57optimization outcomesupports2019Source 1needs review

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.
Claim 58optimization outcomesupports2019Source 1needs review

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.
Claim 59optimization outcomesupports2019Source 1needs review

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.
Claim 60optimization outcomesupports2019Source 1needs review

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.
Claim 61optimization outcomesupports2019Source 1needs review

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 cLIPS2

cLIPS1 and cLIPS2 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

Compared with GLIMPSe

cLIPS1 and GLIMPSe 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

Compared with light-inducible split Cre recombinase

cLIPS1 and light-inducible split Cre recombinase 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

Ranked Citations

  1. 1.
    StructuralSource 1ACS Synthetic Biology2019Claim 1Claim 17Claim 16

    Extracted from this source document.