Source 1primary paper2012The Journal of Chemical Physics
Toolkit/PA-Rac1
PA-Rac1
Also known as: AsLOV2-Jα-regulated photoactivable Rac1-GTPase, photoactivable Rac1-GTPase, photoactivatable form of Rac1, photoactivatable Rac1
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
PA-Rac1 is an AsLOV2-Jα-regulated photoactivable Rac1 GTPase in which light-driven conformational changes in the LOV2 module relieve inhibition at the Rac1 switch II activation site. This release permits effector-protein binding and activates Rac1-associated signaling.
Usefulness & Problems
Why this is useful
PA-Rac1 is useful as a light-responsive switch for controlling Rac1 signaling with a defined mechanistic linkage between the AsLOV2-Jα photosensor and the Rac1 effector-binding interface. The cited evidence also indicates that its signaling behavior is amenable to multiscale computational investigation.
Source:
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
Problem solved
PA-Rac1 addresses the problem of coupling an optical input to conditional activation of a small GTPase signaling protein. Specifically, it provides a design in which illumination-triggered structural changes uncage the Rac1 switch II region and enable downstream effector engagement.
Problem links
Need conditional control of signaling activity
DerivedPA-Rac1 is an AsLOV2-Jα-regulated photoactivable Rac1 GTPase. In the described model, light-driven conformational changes in AsLOV2-Jα release inhibition at the Rac1 switch II activation site, permitting effector-protein binding and signal activation.
Need precise spatiotemporal control with light input
DerivedPA-Rac1 is an AsLOV2-Jα-regulated photoactivable Rac1 GTPase. In the described model, light-driven conformational changes in AsLOV2-Jα release inhibition at the Rac1 switch II activation site, permitting effector-protein binding and signal activation.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Mechanisms
alpha-helix detachmentalpha-helix detachmentautoinhibitory caging and releaseautoinhibitory caging and releaseeffector-binding activationeffector-binding activationlight-induced allosteric switchinglight-induced allosteric switchingTechniques
No technique tags yet.
Target processes
signalingInput: Light
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: multi component delivery burdenimplementation constraint: spectral hardware requirementmodality: optical controloperating role: actuatoroperating role: regulatorswitch architecture: multi componentswitch architecture: uncagingtarget pathway: Rac1 GTPase
PA-Rac1 is described as an AsLOV2-Jα-regulated fusion involving a flavin-mononucleotide chromophore-containing LOV2 photosensory domain linked to Rac1. The evidence supports a construct logic in which the AsLOV2 inhibitor cages the Rac1 switch II activation site until light-induced alpha-helix detachment releases that inhibition, but no expression, delivery, or assay details are given.
The supplied evidence is limited to a mechanistic description and computational suitability from a single 2012 source. No quantitative performance data, illumination parameters, cellular validation, dynamic range, reversibility measurements, or independent experimental replication are provided here.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Source 2primary paper2017Scientific Reports
Ranked Claims
Optical activation of Rac1 using PA-Rac1 in amygdala inhibited long-term but not short-term auditory fear conditioning memory formation.
optical activation of Rac1 GTPase using photoactivatable form of Rac1 (PA-Rac1) in amygdala led to phosphorylation of PAK and inhibition of long-term but not short-term auditory fear conditioning memory formation
Optical activation of Rac1 using PA-Rac1 in amygdala inhibited long-term but not short-term auditory fear conditioning memory formation.
optical activation of Rac1 GTPase using photoactivatable form of Rac1 (PA-Rac1) in amygdala led to phosphorylation of PAK and inhibition of long-term but not short-term auditory fear conditioning memory formation
Optical activation of Rac1 using PA-Rac1 in amygdala inhibited long-term but not short-term auditory fear conditioning memory formation.
optical activation of Rac1 GTPase using photoactivatable form of Rac1 (PA-Rac1) in amygdala led to phosphorylation of PAK and inhibition of long-term but not short-term auditory fear conditioning memory formation
Optical activation of Rac1 using PA-Rac1 in amygdala inhibited long-term but not short-term auditory fear conditioning memory formation.
optical activation of Rac1 GTPase using photoactivatable form of Rac1 (PA-Rac1) in amygdala led to phosphorylation of PAK and inhibition of long-term but not short-term auditory fear conditioning memory formation
Optical activation of Rac1 using PA-Rac1 in amygdala inhibited long-term but not short-term auditory fear conditioning memory formation.
optical activation of Rac1 GTPase using photoactivatable form of Rac1 (PA-Rac1) in amygdala led to phosphorylation of PAK and inhibition of long-term but not short-term auditory fear conditioning memory formation
Optical activation of Rac1 using PA-Rac1 in amygdala led to phosphorylation of PAK.
optical activation of Rac1 GTPase using photoactivatable form of Rac1 (PA-Rac1) in amygdala led to phosphorylation of PAK
Optical activation of Rac1 using PA-Rac1 in amygdala led to phosphorylation of PAK.
optical activation of Rac1 GTPase using photoactivatable form of Rac1 (PA-Rac1) in amygdala led to phosphorylation of PAK
Optical activation of Rac1 using PA-Rac1 in amygdala led to phosphorylation of PAK.
optical activation of Rac1 GTPase using photoactivatable form of Rac1 (PA-Rac1) in amygdala led to phosphorylation of PAK
Optical activation of Rac1 using PA-Rac1 in amygdala led to phosphorylation of PAK.
optical activation of Rac1 GTPase using photoactivatable form of Rac1 (PA-Rac1) in amygdala led to phosphorylation of PAK
Optical activation of Rac1 using PA-Rac1 in amygdala led to phosphorylation of PAK.
optical activation of Rac1 GTPase using photoactivatable form of Rac1 (PA-Rac1) in amygdala led to phosphorylation of PAK
Activation of PA-Rac1 in lateral amygdala one day after fear conditioning had no effect on long-term fear memory tested 24 hours after PA-Rac1 activation.
Activation of PA-Rac1 in LA one day after fear conditioning had no effect on long-term fear memory tested 24 hrs after PA-Rac1 activation.
Activation of PA-Rac1 in lateral amygdala one day after fear conditioning had no effect on long-term fear memory tested 24 hours after PA-Rac1 activation.
Activation of PA-Rac1 in LA one day after fear conditioning had no effect on long-term fear memory tested 24 hrs after PA-Rac1 activation.
Activation of PA-Rac1 in lateral amygdala one day after fear conditioning had no effect on long-term fear memory tested 24 hours after PA-Rac1 activation.
Activation of PA-Rac1 in LA one day after fear conditioning had no effect on long-term fear memory tested 24 hrs after PA-Rac1 activation.
Activation of PA-Rac1 in lateral amygdala one day after fear conditioning had no effect on long-term fear memory tested 24 hours after PA-Rac1 activation.
Activation of PA-Rac1 in LA one day after fear conditioning had no effect on long-term fear memory tested 24 hrs after PA-Rac1 activation.
Activation of PA-Rac1 in lateral amygdala one day after fear conditioning had no effect on long-term fear memory tested 24 hours after PA-Rac1 activation.
Activation of PA-Rac1 in LA one day after fear conditioning had no effect on long-term fear memory tested 24 hrs after PA-Rac1 activation.
In PA-Rac1, detachment of the peripheral alpha-helix induces release of the AsLOV2 inhibitor from the switchII activation site of the GTPase, enabling signal activation through effector-protein binding.
In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding
In PA-Rac1, detachment of the peripheral alpha-helix induces release of the AsLOV2 inhibitor from the switchII activation site of the GTPase, enabling signal activation through effector-protein binding.
In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding
In PA-Rac1, detachment of the peripheral alpha-helix induces release of the AsLOV2 inhibitor from the switchII activation site of the GTPase, enabling signal activation through effector-protein binding.
In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding
In PA-Rac1, detachment of the peripheral alpha-helix induces release of the AsLOV2 inhibitor from the switchII activation site of the GTPase, enabling signal activation through effector-protein binding.
In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding
In PA-Rac1, detachment of the peripheral alpha-helix induces release of the AsLOV2 inhibitor from the switchII activation site of the GTPase, enabling signal activation through effector-protein binding.
In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding
In PA-Rac1, detachment of the peripheral alpha-helix induces release of the AsLOV2 inhibitor from the switchII activation site of the GTPase, enabling signal activation through effector-protein binding.
In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding
In PA-Rac1, detachment of the peripheral alpha-helix induces release of the AsLOV2 inhibitor from the switchII activation site of the GTPase, enabling signal activation through effector-protein binding.
In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding
In PA-Rac1, detachment of the peripheral alpha-helix induces release of the AsLOV2 inhibitor from the switchII activation site of the GTPase, enabling signal activation through effector-protein binding.
In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding
In PA-Rac1, detachment of the peripheral alpha-helix induces release of the AsLOV2 inhibitor from the switchII activation site of the GTPase, enabling signal activation through effector-protein binding.
In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding
In PA-Rac1, detachment of the peripheral alpha-helix induces release of the AsLOV2 inhibitor from the switchII activation site of the GTPase, enabling signal activation through effector-protein binding.
In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding
In PA-Rac1, detachment of the peripheral alpha-helix induces release of the AsLOV2 inhibitor from the switchII activation site of the GTPase, enabling signal activation through effector-protein binding.
In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding
In PA-Rac1, detachment of the peripheral alpha-helix induces release of the AsLOV2 inhibitor from the switchII activation site of the GTPase, enabling signal activation through effector-protein binding.
In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding
In PA-Rac1, detachment of the peripheral alpha-helix induces release of the AsLOV2 inhibitor from the switchII activation site of the GTPase, enabling signal activation through effector-protein binding.
In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding
In PA-Rac1, detachment of the peripheral alpha-helix induces release of the AsLOV2 inhibitor from the switchII activation site of the GTPase, enabling signal activation through effector-protein binding.
In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding
In PA-Rac1, detachment of the peripheral alpha-helix induces release of the AsLOV2 inhibitor from the switchII activation site of the GTPase, enabling signal activation through effector-protein binding.
In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding
In PA-Rac1, detachment of the peripheral alpha-helix induces release of the AsLOV2 inhibitor from the switchII activation site of the GTPase, enabling signal activation through effector-protein binding.
In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding
In PA-Rac1, detachment of the peripheral alpha-helix induces release of the AsLOV2 inhibitor from the switchII activation site of the GTPase, enabling signal activation through effector-protein binding.
In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding
The signaling pathway of AsLOV2-Jα begins with residual rearrangement and subsequent hydrogen-bond formation of amino acids near the flavin-mononucleotide chromophore, causing coupling between beta-strands and subsequent detachment of a peripheral alpha-helix from the AsLOV2 domain.
their signaling pathways begin with a residual re-arrangement and subsequent H-bond formation of amino acids near to the flavin-mononucleotide chromophore, causing a coupling between β-strands and subsequent detachment of a peripheral α-helix from the AsLOV2-domain
The signaling pathway of AsLOV2-Jα begins with residual rearrangement and subsequent hydrogen-bond formation of amino acids near the flavin-mononucleotide chromophore, causing coupling between beta-strands and subsequent detachment of a peripheral alpha-helix from the AsLOV2 domain.
their signaling pathways begin with a residual re-arrangement and subsequent H-bond formation of amino acids near to the flavin-mononucleotide chromophore, causing a coupling between β-strands and subsequent detachment of a peripheral α-helix from the AsLOV2-domain
The signaling pathway of AsLOV2-Jα begins with residual rearrangement and subsequent hydrogen-bond formation of amino acids near the flavin-mononucleotide chromophore, causing coupling between beta-strands and subsequent detachment of a peripheral alpha-helix from the AsLOV2 domain.
their signaling pathways begin with a residual re-arrangement and subsequent H-bond formation of amino acids near to the flavin-mononucleotide chromophore, causing a coupling between β-strands and subsequent detachment of a peripheral α-helix from the AsLOV2-domain
The signaling pathway of AsLOV2-Jα begins with residual rearrangement and subsequent hydrogen-bond formation of amino acids near the flavin-mononucleotide chromophore, causing coupling between beta-strands and subsequent detachment of a peripheral alpha-helix from the AsLOV2 domain.
their signaling pathways begin with a residual re-arrangement and subsequent H-bond formation of amino acids near to the flavin-mononucleotide chromophore, causing a coupling between β-strands and subsequent detachment of a peripheral α-helix from the AsLOV2-domain
The signaling pathway of AsLOV2-Jα begins with residual rearrangement and subsequent hydrogen-bond formation of amino acids near the flavin-mononucleotide chromophore, causing coupling between beta-strands and subsequent detachment of a peripheral alpha-helix from the AsLOV2 domain.
their signaling pathways begin with a residual re-arrangement and subsequent H-bond formation of amino acids near to the flavin-mononucleotide chromophore, causing a coupling between β-strands and subsequent detachment of a peripheral α-helix from the AsLOV2-domain
The signaling pathway of AsLOV2-Jα begins with residual rearrangement and subsequent hydrogen-bond formation of amino acids near the flavin-mononucleotide chromophore, causing coupling between beta-strands and subsequent detachment of a peripheral alpha-helix from the AsLOV2 domain.
their signaling pathways begin with a residual re-arrangement and subsequent H-bond formation of amino acids near to the flavin-mononucleotide chromophore, causing a coupling between β-strands and subsequent detachment of a peripheral α-helix from the AsLOV2-domain
The signaling pathway of AsLOV2-Jα begins with residual rearrangement and subsequent hydrogen-bond formation of amino acids near the flavin-mononucleotide chromophore, causing coupling between beta-strands and subsequent detachment of a peripheral alpha-helix from the AsLOV2 domain.
their signaling pathways begin with a residual re-arrangement and subsequent H-bond formation of amino acids near to the flavin-mononucleotide chromophore, causing a coupling between β-strands and subsequent detachment of a peripheral α-helix from the AsLOV2-domain
The signaling pathway of AsLOV2-Jα begins with residual rearrangement and subsequent hydrogen-bond formation of amino acids near the flavin-mononucleotide chromophore, causing coupling between beta-strands and subsequent detachment of a peripheral alpha-helix from the AsLOV2 domain.
their signaling pathways begin with a residual re-arrangement and subsequent H-bond formation of amino acids near to the flavin-mononucleotide chromophore, causing a coupling between β-strands and subsequent detachment of a peripheral α-helix from the AsLOV2-domain
The signaling pathway of AsLOV2-Jα begins with residual rearrangement and subsequent hydrogen-bond formation of amino acids near the flavin-mononucleotide chromophore, causing coupling between beta-strands and subsequent detachment of a peripheral alpha-helix from the AsLOV2 domain.
their signaling pathways begin with a residual re-arrangement and subsequent H-bond formation of amino acids near to the flavin-mononucleotide chromophore, causing a coupling between β-strands and subsequent detachment of a peripheral α-helix from the AsLOV2-domain
The signaling pathway of AsLOV2-Jα begins with residual rearrangement and subsequent hydrogen-bond formation of amino acids near the flavin-mononucleotide chromophore, causing coupling between beta-strands and subsequent detachment of a peripheral alpha-helix from the AsLOV2 domain.
their signaling pathways begin with a residual re-arrangement and subsequent H-bond formation of amino acids near to the flavin-mononucleotide chromophore, causing a coupling between β-strands and subsequent detachment of a peripheral α-helix from the AsLOV2-domain
The multiscale-modeling method is suitable for investigating the signaling behavior of AsLOV2-Jα and PA-Rac1.
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
The multiscale-modeling method is suitable for investigating the signaling behavior of AsLOV2-Jα and PA-Rac1.
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
The multiscale-modeling method is suitable for investigating the signaling behavior of AsLOV2-Jα and PA-Rac1.
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
The multiscale-modeling method is suitable for investigating the signaling behavior of AsLOV2-Jα and PA-Rac1.
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
The multiscale-modeling method is suitable for investigating the signaling behavior of AsLOV2-Jα and PA-Rac1.
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
The multiscale-modeling method is suitable for investigating the signaling behavior of AsLOV2-Jα and PA-Rac1.
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
The multiscale-modeling method is suitable for investigating the signaling behavior of AsLOV2-Jα and PA-Rac1.
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
The multiscale-modeling method is suitable for investigating the signaling behavior of AsLOV2-Jα and PA-Rac1.
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
The multiscale-modeling method is suitable for investigating the signaling behavior of AsLOV2-Jα and PA-Rac1.
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
The multiscale-modeling method is suitable for investigating the signaling behavior of AsLOV2-Jα and PA-Rac1.
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
The multiscale-modeling method is suitable for investigating the signaling behavior of AsLOV2-Jα and PA-Rac1.
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
The multiscale-modeling method is suitable for investigating the signaling behavior of AsLOV2-Jα and PA-Rac1.
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
The multiscale-modeling method is suitable for investigating the signaling behavior of AsLOV2-Jα and PA-Rac1.
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
The multiscale-modeling method is suitable for investigating the signaling behavior of AsLOV2-Jα and PA-Rac1.
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
The multiscale-modeling method is suitable for investigating the signaling behavior of AsLOV2-Jα and PA-Rac1.
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
The multiscale-modeling method is suitable for investigating the signaling behavior of AsLOV2-Jα and PA-Rac1.
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
The multiscale-modeling method is suitable for investigating the signaling behavior of AsLOV2-Jα and PA-Rac1.
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
Approval Evidence
2 sources5 linked approval claimsfirst-pass slug pa-rac1
optical activation of Rac1 GTPase using photoactivatable form of Rac1 (PA-Rac1) in amygdala
Source:
an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
Source:
behavioral effectsupports
Optical activation of Rac1 using PA-Rac1 in amygdala inhibited long-term but not short-term auditory fear conditioning memory formation.
optical activation of Rac1 GTPase using photoactivatable form of Rac1 (PA-Rac1) in amygdala led to phosphorylation of PAK and inhibition of long-term but not short-term auditory fear conditioning memory formation
Source:
mechanistic effectsupports
Optical activation of Rac1 using PA-Rac1 in amygdala led to phosphorylation of PAK.
optical activation of Rac1 GTPase using photoactivatable form of Rac1 (PA-Rac1) in amygdala led to phosphorylation of PAK
Source:
timing dependencesupports
Activation of PA-Rac1 in lateral amygdala one day after fear conditioning had no effect on long-term fear memory tested 24 hours after PA-Rac1 activation.
Activation of PA-Rac1 in LA one day after fear conditioning had no effect on long-term fear memory tested 24 hrs after PA-Rac1 activation.
Source:
mechanistic pathwaysupports
In PA-Rac1, detachment of the peripheral alpha-helix induces release of the AsLOV2 inhibitor from the switchII activation site of the GTPase, enabling signal activation through effector-protein binding.
In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding
Source:
method capabilitysupports
The multiscale-modeling method is suitable for investigating the signaling behavior of AsLOV2-Jα and PA-Rac1.
we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1)
Source:
Comparisons
Source-backed strengths
The available evidence provides a mechanistic model that connects chromophore-proximal rearrangements in AsLOV2-Jα to beta-strand coupling, peripheral alpha-helix detachment, inhibitor release, and Rac1 effector-binding activation. The tool is also explicitly identified as suitable for analysis by a multiscale-modeling framework.
Compared with AsLOV2-Jα-Rac1
PA-Rac1 and AsLOV2-Jα-Rac1 address a similar problem space because they share signaling.
Shared frame: same top-level item type; shared target processes: signaling; shared mechanisms: light-induced allosteric switching; same primary input modality: light
Compared with caging/uncaging events
PA-Rac1 and caging/uncaging events address a similar problem space because they share signaling.
Shared frame: same top-level item type; shared target processes: signaling; same primary input modality: light
Compared with PiL[D24]
PA-Rac1 and PiL[D24] address a similar problem space because they share signaling.
Shared frame: same top-level item type; shared target processes: signaling; shared mechanisms: light-induced allosteric switching; same primary input modality: light
Ranked Citations
- 1.
- 2.