Source 1primary paper2021Nature Communications
Toolkit/two-input protein logic OR gate
two-input protein logic OR gate
Also known as: engineered, single protein design, two-input logic OR gate
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
The two-input protein logic OR gate is an engineered single-protein focal adhesion kinase (FAK) system designed to integrate chemical and optical inputs within the native FAK domain architecture. It functions as an allosterically regulated OR gate by combining a rapamycin-inducible uniRapR module in the kinase domain with a light-inducible LOV2 module in the FERM domain.
Usefulness & Problems
Why this is useful
This tool is useful for implementing protein-level computation in living cells using orthogonal chemo-optogenetic control. In the reported system, 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 integrating two distinct external inputs into a single engineered signaling protein while retaining the underlying FAK domain architecture. The reported design specifically enables OR-gate control of FAK activity through chemical and optical regulation.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Mechanisms
allosteric regulationconformational uncagingConformational Uncagingorthogonal chemo-optogenetic controlTechniques
Computational DesignTarget processes
No target processes tagged yet.
Implementation Constraints
The reported construct places a rapamycin-inducible uniRapR module in the FAK kinase domain and a light-inducible LOV2 module in the FERM domain while retaining FAK domain architecture. Practical implementation therefore requires rapamycin as the chemical input and optical stimulation of the LOV2-containing module, but the supplied evidence does not specify expression system details or illumination parameters.
The supplied evidence is limited to a single 2021 source and does not provide quantitative performance metrics such as activation dynamic range, response kinetics, leakiness, or reversibility. Evidence for validation across multiple cell types, organisms, or independent studies is not 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 source2 linked approval claimsfirst-pass slug two-input-protein-logic-or-gate
we report an engineered, single protein design that is allosterically regulated to function as a 'two-input logic OR gate'
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:
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 embeds both rapamycin-inducible and light-inducible control modules in a single FAK protein and was reported to operate as a two-input logic OR gate. It was also linked to measurable cellular effects, with dynamic FAK activation increasing cell multiaxial complexity and decreasing motility in a fibrous extracellular matrix setting.
Ranked Citations
- 1.