Source 1primary paper2021Nature Communications
Toolkit/engineered focal adhesion kinase two-input gate
engineered focal adhesion kinase two-input gate
Also known as: engineered FAK
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
The engineered focal adhesion kinase (FAK) is a single-protein, two-input logic OR gate that integrates chemogenetic and optogenetic control within the native FAK domain architecture. It places a rapamycin-inducible uniRapR module in the kinase domain and a light-inducible LOV2 module in the FERM domain to allosterically regulate FAK activity.
Usefulness & Problems
Why this is useful
This tool enables combinatorial control of a signaling protein within one polypeptide rather than requiring multi-component assemblies. In the reported study, dynamic FAK activation altered cell behavior in a fibrous extracellular matrix microenvironment, increasing multiaxial complexity and decreasing motility.
Problem solved
It addresses the problem of building protein-based logic computation directly into a native signaling protein while preserving overall domain architecture. The reported design specifically implements two-input OR-gate control over FAK through chemical and light-responsive allosteric regulation.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Mechanisms
allosteric switchingchemically induced regulationconformational uncagingConformational Uncaginglight-induced regulationTechniques
Computational DesignTarget processes
recombinationsignalingInput: Light
Implementation Constraints
The construct is a single engineered FAK protein containing a uniRapR module in the kinase domain and a LOV2 module in the FERM domain. Its operation depends on rapamycin for chemogenetic input and light for optogenetic input, but the supplied evidence does not specify illumination wavelength, expression system, or delivery method.
The supplied evidence does not provide quantitative performance metrics such as activation dynamic range, kinetics, leakiness, or reversibility. Validation described here is limited to the reported engineered function and a specific cell-behavior phenotype, with no independent replication provided.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Dynamic FAK activation increased cell multiaxial complexity in a fibrous extracellular matrix microenvironment and decreased cell motility.
We demonstrate that dynamic FAK activation profoundly increased cell multiaxial complexity in the fibrous extracellular matrix microenvironment and decreased cell motility.
Dynamic FAK activation increased cell multiaxial complexity in a fibrous extracellular matrix microenvironment and decreased cell motility.
We demonstrate that dynamic FAK activation profoundly increased cell multiaxial complexity in the fibrous extracellular matrix microenvironment and decreased cell motility.
Dynamic FAK activation increased cell multiaxial complexity in a fibrous extracellular matrix microenvironment and decreased cell motility.
We demonstrate that dynamic FAK activation profoundly increased cell multiaxial complexity in the fibrous extracellular matrix microenvironment and decreased cell motility.
Dynamic FAK activation increased cell multiaxial complexity in a fibrous extracellular matrix microenvironment and decreased cell motility.
We demonstrate that dynamic FAK activation profoundly increased cell multiaxial complexity in the fibrous extracellular matrix microenvironment and decreased cell motility.
Dynamic FAK activation increased cell multiaxial complexity in a fibrous extracellular matrix microenvironment and decreased cell motility.
We demonstrate that dynamic FAK activation profoundly increased cell multiaxial complexity in the fibrous extracellular matrix microenvironment and decreased cell motility.
Dynamic FAK activation increased cell multiaxial complexity in a fibrous extracellular matrix microenvironment and decreased cell motility.
We demonstrate that dynamic FAK activation profoundly increased cell multiaxial complexity in the fibrous extracellular matrix microenvironment and decreased cell motility.
Dynamic FAK activation increased cell multiaxial complexity in a fibrous extracellular matrix microenvironment and decreased cell motility.
We demonstrate that dynamic FAK activation profoundly increased cell multiaxial complexity in the fibrous extracellular matrix microenvironment and decreased cell motility.
The engineered focal adhesion kinase system uses chemo- and optogenetic regulation with a rapamycin-inducible uniRapR module in the kinase domain and a light-inducible LOV2 module in the FERM domain while retaining FAK domain architecture.
Our system is based on chemo- and optogenetic regulation of focal adhesion kinase. In the engineered FAK, all of FAK domain architecture is retained and key intramolecular interactions between the kinase and the FERM domains are externally controlled through a rapamycin-inducible uniRapR module in the kinase domain and a light-inducible LOV2 module in the FERM domain.
The engineered focal adhesion kinase system uses chemo- and optogenetic regulation with a rapamycin-inducible uniRapR module in the kinase domain and a light-inducible LOV2 module in the FERM domain while retaining FAK domain architecture.
Our system is based on chemo- and optogenetic regulation of focal adhesion kinase. In the engineered FAK, all of FAK domain architecture is retained and key intramolecular interactions between the kinase and the FERM domains are externally controlled through a rapamycin-inducible uniRapR module in the kinase domain and a light-inducible LOV2 module in the FERM domain.
The engineered focal adhesion kinase system uses chemo- and optogenetic regulation with a rapamycin-inducible uniRapR module in the kinase domain and a light-inducible LOV2 module in the FERM domain while retaining FAK domain architecture.
Our system is based on chemo- and optogenetic regulation of focal adhesion kinase. In the engineered FAK, all of FAK domain architecture is retained and key intramolecular interactions between the kinase and the FERM domains are externally controlled through a rapamycin-inducible uniRapR module in the kinase domain and a light-inducible LOV2 module in the FERM domain.
The engineered focal adhesion kinase system uses chemo- and optogenetic regulation with a rapamycin-inducible uniRapR module in the kinase domain and a light-inducible LOV2 module in the FERM domain while retaining FAK domain architecture.
Our system is based on chemo- and optogenetic regulation of focal adhesion kinase. In the engineered FAK, all of FAK domain architecture is retained and key intramolecular interactions between the kinase and the FERM domains are externally controlled through a rapamycin-inducible uniRapR module in the kinase domain and a light-inducible LOV2 module in the FERM domain.
The engineered focal adhesion kinase system uses chemo- and optogenetic regulation with a rapamycin-inducible uniRapR module in the kinase domain and a light-inducible LOV2 module in the FERM domain while retaining FAK domain architecture.
Our system is based on chemo- and optogenetic regulation of focal adhesion kinase. In the engineered FAK, all of FAK domain architecture is retained and key intramolecular interactions between the kinase and the FERM domains are externally controlled through a rapamycin-inducible uniRapR module in the kinase domain and a light-inducible LOV2 module in the FERM domain.
The engineered focal adhesion kinase system uses chemo- and optogenetic regulation with a rapamycin-inducible uniRapR module in the kinase domain and a light-inducible LOV2 module in the FERM domain while retaining FAK domain architecture.
Our system is based on chemo- and optogenetic regulation of focal adhesion kinase. In the engineered FAK, all of FAK domain architecture is retained and key intramolecular interactions between the kinase and the FERM domains are externally controlled through a rapamycin-inducible uniRapR module in the kinase domain and a light-inducible LOV2 module in the FERM domain.
The engineered focal adhesion kinase system uses chemo- and optogenetic regulation with a rapamycin-inducible uniRapR module in the kinase domain and a light-inducible LOV2 module in the FERM domain while retaining FAK domain architecture.
Our system is based on chemo- and optogenetic regulation of focal adhesion kinase. In the engineered FAK, all of FAK domain architecture is retained and key intramolecular interactions between the kinase and the FERM domains are externally controlled through a rapamycin-inducible uniRapR module in the kinase domain and a light-inducible LOV2 module in the FERM domain.
An engineered single protein design was allosterically regulated to function as a two-input logic OR gate.
we report an engineered, single protein design that is allosterically regulated to function as a 'two-input logic OR gate'
An engineered single protein design was allosterically regulated to function as a two-input logic OR gate.
we report an engineered, single protein design that is allosterically regulated to function as a 'two-input logic OR gate'
An engineered single protein design was allosterically regulated to function as a two-input logic OR gate.
we report an engineered, single protein design that is allosterically regulated to function as a 'two-input logic OR gate'
An engineered single protein design was allosterically regulated to function as a two-input logic OR gate.
we report an engineered, single protein design that is allosterically regulated to function as a 'two-input logic OR gate'
An engineered single protein design was allosterically regulated to function as a two-input logic OR gate.
we report an engineered, single protein design that is allosterically regulated to function as a 'two-input logic OR gate'
An engineered single protein design was allosterically regulated to function as a two-input logic OR gate.
we report an engineered, single protein design that is allosterically regulated to function as a 'two-input logic OR gate'
An engineered single protein design was allosterically regulated to function as a two-input logic OR gate.
we report an engineered, single protein design that is allosterically regulated to function as a 'two-input logic OR gate'
Chemo- and optogenetic switches enabled orthogonal regulation of protein function in the engineered system.
Orthogonal regulation of protein function was possible using the chemo- and optogenetic switches.
Chemo- and optogenetic switches enabled orthogonal regulation of protein function in the engineered system.
Orthogonal regulation of protein function was possible using the chemo- and optogenetic switches.
Chemo- and optogenetic switches enabled orthogonal regulation of protein function in the engineered system.
Orthogonal regulation of protein function was possible using the chemo- and optogenetic switches.
Chemo- and optogenetic switches enabled orthogonal regulation of protein function in the engineered system.
Orthogonal regulation of protein function was possible using the chemo- and optogenetic switches.
Chemo- and optogenetic switches enabled orthogonal regulation of protein function in the engineered system.
Orthogonal regulation of protein function was possible using the chemo- and optogenetic switches.
Chemo- and optogenetic switches enabled orthogonal regulation of protein function in the engineered system.
Orthogonal regulation of protein function was possible using the chemo- and optogenetic switches.
Chemo- and optogenetic switches enabled orthogonal regulation of protein function in the engineered system.
Orthogonal regulation of protein function was possible using the chemo- and optogenetic switches.
The work provides proof-of-principle for fine multimodal control of protein function.
This work provides proof-of-principle for fine multimodal control of protein function
The work provides proof-of-principle for fine multimodal control of protein function.
This work provides proof-of-principle for fine multimodal control of protein function
The work provides proof-of-principle for fine multimodal control of protein function.
This work provides proof-of-principle for fine multimodal control of protein function
The work provides proof-of-principle for fine multimodal control of protein function.
This work provides proof-of-principle for fine multimodal control of protein function
The work provides proof-of-principle for fine multimodal control of protein function.
This work provides proof-of-principle for fine multimodal control of protein function
The work provides proof-of-principle for fine multimodal control of protein function.
This work provides proof-of-principle for fine multimodal control of protein function
The work provides proof-of-principle for fine multimodal control of protein function.
This work provides proof-of-principle for fine multimodal control of protein function
Approval Evidence
1 source5 linked approval claimsfirst-pass slug engineered-focal-adhesion-kinase-two-input-gate
Our system is based on chemo- and optogenetic regulation of focal adhesion kinase. In the engineered FAK, all of FAK domain architecture is retained
Source:
cellular effectsupports
Dynamic FAK activation increased cell multiaxial complexity in a fibrous extracellular matrix microenvironment and decreased cell motility.
We demonstrate that dynamic FAK activation profoundly increased cell multiaxial complexity in the fibrous extracellular matrix microenvironment and decreased cell motility.
Source:
design architecturesupports
The engineered focal adhesion kinase system uses chemo- and optogenetic regulation with a rapamycin-inducible uniRapR module in the kinase domain and a light-inducible LOV2 module in the FERM domain while retaining FAK domain architecture.
Our system is based on chemo- and optogenetic regulation of focal adhesion kinase. In the engineered FAK, all of FAK domain architecture is retained and key intramolecular interactions between the kinase and the FERM domains are externally controlled through a rapamycin-inducible uniRapR module in the kinase domain and a light-inducible LOV2 module in the FERM domain.
Source:
engineered functionsupports
An engineered single protein design was allosterically regulated to function as a two-input logic OR gate.
we report an engineered, single protein design that is allosterically regulated to function as a 'two-input logic OR gate'
Source:
orthogonal regulationsupports
Chemo- and optogenetic switches enabled orthogonal regulation of protein function in the engineered system.
Orthogonal regulation of protein function was possible using the chemo- and optogenetic switches.
Source:
proof of principlesupports
The work provides proof-of-principle for fine multimodal control of protein function.
This work provides proof-of-principle for fine multimodal control of protein function
Source:
Comparisons
Source-backed strengths
The design retains the overall FAK domain architecture while introducing both rapamycin-responsive and light-responsive control elements. It was reported to function as an allosterically regulated two-input OR gate, and dynamic activation produced measurable cellular phenotypes in a fibrous extracellular matrix context.
Ranked Citations
- 1.