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Published on: January 19, 2015
CRIB effector disorder: exquisite function from chaos
1Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, U.K. do202@cam.ac.uk.
Insights
Cdc42/Rac interactive binding (CRIB) proteins utilize intrinsically disordered regions and basic regions to bind G-proteins. This interaction drives liquid-liquid phase separation, crucial for forming cellular signalosomes.
Area of Science:
- Molecular and Cellular Biology
- Biochemistry
- Structural Biology
Background:
- Cdc42/Rac interactive binding (CRIB) proteins are effectors of small G-proteins.
- These proteins feature intrinsically disordered regions (IDRs) and basic regions (BRs).
Purpose of the Study:
- To elucidate the structural and functional roles of IDRs and BRs in CRIB proteins.
- To understand how these regions mediate G-protein binding and signalosome formation.
Main Methods:
- Analysis of protein structure and disorder.
- Investigation of protein-protein interactions.
- Studies on liquid-liquid phase separation.
Main Results:
- G-protein binding regions within CRIB proteins are intrinsically disordered.
- Basic regions in CRIB proteins facilitate G-protein binding via a dock-and-coalesce mechanism.
- Intrinsically disordered regions and basic regions enable multivalent interactions, driving liquid-liquid phase separation and signalosome assembly.
Conclusions:
- The structural plasticity of CRIB proteins, particularly their IDRs and BRs, is essential for their function.
- These features allow CRIB proteins to mediate G-protein interactions and initiate signalosome formation through liquid-liquid phase separation.
Abstract:
The CRIB (Cdc42/Rac interactive binding) family of small G-protein effectors contain significant regions with intrinsic disorder. The G-protein-binding regions are contained within these intrinsically disordered regions. Most CRIB proteins also contain stretches of basic residues associated with their G-protein-binding regions. The basic region (BR) and G-protein-binding region together allow the CRIB effectors to bind to their cognate G-protein via a dock- and coalesce-binding mechanism. The BRs of these proteins take on multiple roles: steering G-protein binding, interacting with elements of the membrane and regulating intramolecular regulatory interactions. The ability of these regions of the CRIBs to undergo multivalent interactions and mediate charge neutralizations equips them with all the properties required to drive liquid-liquid phase separation and therefore to initiate and drive signalosome formation. It is only recently that the structural plasticity in these proteins is being appreciated as the driving force for these vital cellular processes.
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