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Allostery and dynamics in small G proteins.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Mott, Helen R 

Abstract

The Ras family of small guanine nucleotide-binding proteins behave as molecular switches: they are switched off and inactive when bound to GDP but can be activated by GTP binding in response to signal transduction pathways. Early structural analysis showed that two regions of the protein, which change conformation depending on the nucleotide present, mediate this switch. A large number of X-ray, NMR and simulation studies have shown that this is an over-simplification. The switch regions themselves are highly dynamic and can exist in distinct sub-states in the GTP-bound form that have different affinities for other proteins. Furthermore, regions outside the switches have been found to be sensitive to the nucleotide state of the protein, indicating that allosteric change is more widespread than previously thought. Taken together, the accrued knowledge about small G protein structures, allostery and dynamics will be essential for the design and testing of the next generation of inhibitors, both orthosteric and allosteric, as well as for understanding their mode of action.

Description

Keywords

NMR spectroscopy, allostery, dynamics, small G proteins, Allosteric Site, Guanine Nucleotide Exchange Factors, Guanosine Diphosphate, Guanosine Triphosphate, Monomeric GTP-Binding Proteins, Mutation, Protein Binding, Protein Domains, Protein Structure, Secondary, Signal Transduction

Journal Title

Biochem Soc Trans

Conference Name

Journal ISSN

0300-5127
1470-8752

Volume Title

46

Publisher

Portland Press Ltd.