Source 1primary paper2015ChemBioChem
Toolkit/hybrid phototropin LOV2 domains incorporating the BID BH3 region
hybrid phototropin LOV2 domains incorporating the BID BH3 region
Also known as: designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of BID, light-dependent optogenetic tool
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Hybrid phototropin LOV2 domains were engineered to incorporate the BID Bcl homology region 3 (BH3), creating a light-dependent optogenetic switch. Illumination induces LOV2 conformational changes that expose the BH3 element and modulate binding to the anti-apoptotic Bcl-2 family protein Bcl-xL.
Usefulness & Problems
Why this is useful
This tool provides optical control over a specific protein-protein interaction involving the BID BH3 motif and Bcl-xL. It is useful for studying and perturbing Bcl-2 family interactions with light-dependent temporal control.
Source:
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
Problem solved
It addresses the problem of conditionally exposing a pro-apoptotic BH3 peptide sequence so that interaction with Bcl-xL can be regulated by light rather than remaining constitutively available. The evidence supports modulation of Bcl-xL binding, but does not establish broader functional outputs beyond this interaction.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Mechanisms
conformational uncagingConformational Uncagingcovalent cysteinyl-flavin adduct formationlight-dependent modulation of protein-protein interactionTechniques
Computational DesignTarget processes
recombinationInput: Light
Implementation Constraints
The construct is a hybrid domain fusion in which the BID BH3 region is incorporated into a phototropin LOV2 scaffold. Its photoswitching mechanism depends on covalent cysteinyl-flavin adduct formation and signal propagation through hydrogen-bonding networks in the LOV2 protein core.
The available evidence is limited to a single cited study and focuses on mechanism and interaction modulation with Bcl-xL. The provided evidence does not report independent replication, quantitative performance metrics, wavelength details, or validation across multiple biological contexts.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
Approval Evidence
1 source2 linked approval claimsfirst-pass slug hybrid-phototropin-lov2-domains-incorporating-the-bid-bh3-region
designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID)
Source:
functionsupports
The conformational change of a flanking amphiphilic alpha-helix in the hybrid LOV2-BH3 construct creates a light-dependent optogenetic tool that modulates interactions with the anti-apoptotic Bcl-2 family member Bcl-xL.
The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
Source:
mechanismsupports
In designed hybrid phototropin LOV2 domains incorporating the BID BH3 region, conformational changes triggered by covalent cysteinyl flavin adduct formation are propagated through hydrogen-bonding networks in the protein core.
Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID).
Source:
Comparisons
Source-backed strengths
The design couples a defined LOV2 photosensory conformational response to exposure of an embedded BH3 sequence. Source claims indicate that light-dependent modulation of Bcl-xL interaction is achieved through the flanking amphiphilic alpha-helix and LOV2 core signaling pathway.
Ranked Citations
- 1.