Source 1primary paper2021Nature Communications
Toolkit/uniRapR module
uniRapR module
Also known as: rapamycin-inducible uniRapR module
Taxonomy: Mechanism Branch / Component. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
The uniRapR module is a rapamycin-inducible protein domain inserted into the kinase domain of engineered focal adhesion kinase (FAK). In the reported 2021 system, it provided allosteric chemical control as one input of a single-protein two-input OR gate that also contained a light-responsive LOV2 module in the FERM domain.
Usefulness & Problems
Why this is useful
This module is useful for building chemically controllable signaling proteins while preserving the overall domain architecture of the host protein. In the reported FAK design, it enabled orthogonal chemo-optogenetic regulation within a single engineered protein for cellular computation.
Problem solved
The reported design addresses the problem of integrating multiple external inputs into one signaling protein to achieve logic-gated control of activity. Specifically, the uniRapR insertion contributed a rapamycin-responsive input to an allosterically regulated FAK OR gate.
Problem links
Need conditional control of signaling activity
DerivedThe uniRapR module is a rapamycin-inducible protein domain inserted into the kinase domain of engineered focal adhesion kinase (FAK). In the reported system, it contributes allosteric chemical control of FAK within a single-protein two-input OR gate that also includes a LOV2 light-responsive module in the FERM domain.
Need precise spatiotemporal control with light input
DerivedThe uniRapR module is a rapamycin-inducible protein domain inserted into the kinase domain of engineered focal adhesion kinase (FAK). In the reported system, it contributes allosteric chemical control of FAK within a single-protein two-input OR gate that also includes a LOV2 light-responsive module in the FERM domain.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Component: A low-level protein part used inside a larger architecture that realizes a mechanism.
Mechanisms
allosteric switchingallosteric switchingorthogonal multi-input regulationorthogonal multi-input regulationrapamycin-inducible regulationrapamycin-inducible regulationTechniques
No technique tags yet.
Target processes
signalingInput: Light
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: spectral hardware requirementoperating role: actuatoroperating role: regulatorswitch architecture: uncaging
The available evidence places the uniRapR module in the kinase domain of engineered FAK, while a LOV2 module was placed in the FERM domain, and the overall FAK domain architecture was retained. Rapamycin is the stated chemical input, but the supplied evidence does not provide construct boundaries, insertion sites, dosing conditions, or expression details.
The supplied evidence is limited to one reported application in engineered FAK and does not define the module's standalone performance, kinetics, dynamic range, or transferability to other proteins. Independent replication and broader validation beyond this architecture are not provided in the supplied evidence.
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.
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.
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.
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'
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.
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.
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
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 unirapr-module
a rapamycin-inducible uniRapR module in the kinase domain
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:
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:
Comparisons
Source-backed strengths
Evidence supports that the uniRapR module functioned within a single-protein, allosterically regulated two-input OR gate together with LOV2. In the engineered FAK context, dynamic activation was associated with increased cell multiaxial complexity in fibrous extracellular matrix and decreased cell motility.
Compared with AsLOV2-Jα
uniRapR module and AsLOV2-Jα address a similar problem space because they share signaling.
Shared frame: same top-level item type; shared target processes: signaling; shared mechanisms: allosteric switching; same primary input modality: light
Relative tradeoffs: appears more independently replicated; looks easier to implement in practice.
Compared with LOV2 module
uniRapR module and LOV2 module address a similar problem space because they share signaling.
Shared frame: same top-level item type; shared target processes: signaling; shared mechanisms: allosteric switching, orthogonal multi-input regulation; same primary input modality: light
uniRapR module and photoactivatable inhibitor for cyclic-AMP dependent kinase (PKA) address a similar problem space because they share signaling.
Shared frame: same top-level item type; shared target processes: signaling; shared mechanisms: allosteric switching; same primary input modality: light
Ranked Citations
- 1.