Source 1primary paper2025MED
Toolkit/PRCIS
PRCIS
Also known as: protease-responsive conformationally inhibited system
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Here, we report the design of a protease-responsive conformationally inhibited system (PRCIS). By intramolecularly linking the free DNA-binding domains of ATF to confined dimerized regions, the transcriptional binding is conformationally inactivated. The function of DNA binding is reinstated upon proteolytic cleavage of linkages, activating the downstream gene expressions.
Usefulness & Problems
No literature-backed usefulness or problem-fit explainer has been materialized for this record yet.
Published Workflows
Objective: Design a generalizable protease-responsive artificial transcription factor system that keeps ATF DNA binding inactive until proteolytic cleavage and then activates downstream gene expression, while supporting orthogonal and composable synthetic regulation.
Why it works: The design works by physically constraining ATF DNA-binding domains through intramolecular linkage to confined dimerized regions so that transcriptional binding is off until a protease cleaves the linkage and releases the inhibited state.
conformational inhibition of ATF DNA bindingproteolytic cleavage-mediated restoration of DNA bindingdownstream gene expression activationmodular ATF designsynthetic circuit construction
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Mechanisms
conformational uncagingConformational Uncagingdna bindingDNA BindingHeterodimerizationPhotocleavageproteolytic cleavageTechniques
Computational DesignTarget processes
transcriptionInput: Chemical
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
PRCIS was developed into triple-orthogonal protease-responsive platforms, dual-orthogonal chemical-inducible platforms, and Boolean logic operations.
the development of PRCIS-based triple-orthogonal protease-responsive and dual-orthogonal chemical-inducible platforms and Boolean logic operations are elaborated in this paper
PRCIS is adaptable to various ATFs and proteases.
The versatility of PRCIS design is demonstrated through its adaptability to various ATFs and proteases
PRCIS conformationally inactivates ATF DNA binding by intramolecularly linking free DNA-binding domains to confined dimerized regions, and proteolytic cleavage restores DNA binding to activate downstream gene expression.
By intramolecularly linking the free DNA-binding domains of ATF to confined dimerized regions, the transcriptional binding is conformationally inactivated. The function of DNA binding is reinstated upon proteolytic cleavage of linkages, activating the downstream gene expressions.
PRCIS shows high activation ratios and specificity.
showcasing high activation ratios and specificity
Approval Evidence
1 source4 linked approval claimsfirst-pass slug prcis
Here, we report the design of a protease-responsive conformationally inhibited system (PRCIS). By intramolecularly linking the free DNA-binding domains of ATF to confined dimerized regions, the transcriptional binding is conformationally inactivated. The function of DNA binding is reinstated upon proteolytic cleavage of linkages, activating the downstream gene expressions.
Source:
applicationsupports
PRCIS was developed into triple-orthogonal protease-responsive platforms, dual-orthogonal chemical-inducible platforms, and Boolean logic operations.
the development of PRCIS-based triple-orthogonal protease-responsive and dual-orthogonal chemical-inducible platforms and Boolean logic operations are elaborated in this paper
Source:
generalizabilitysupports
PRCIS is adaptable to various ATFs and proteases.
The versatility of PRCIS design is demonstrated through its adaptability to various ATFs and proteases
Source:
mechanismsupports
PRCIS conformationally inactivates ATF DNA binding by intramolecularly linking free DNA-binding domains to confined dimerized regions, and proteolytic cleavage restores DNA binding to activate downstream gene expression.
By intramolecularly linking the free DNA-binding domains of ATF to confined dimerized regions, the transcriptional binding is conformationally inactivated. The function of DNA binding is reinstated upon proteolytic cleavage of linkages, activating the downstream gene expressions.
Source:
performancesupports
PRCIS shows high activation ratios and specificity.
showcasing high activation ratios and specificity
Source:
Comparisons
No literature-backed comparison notes have been materialized for this record yet.
Ranked Citations
- 1.