Allostery and dynamics in small G proteins.
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Publication Date
2018-10-19Journal Title
Biochem Soc Trans
ISSN
0300-5127
Publisher
Portland Press Ltd.
Volume
46
Issue
5
Pages
1333-1343
Language
eng
Type
Article
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Mott, H., & Owen, D. (2018). Allostery and dynamics in small G proteins.. Biochem Soc Trans, 46 (5), 1333-1343. https://doi.org/10.1042/BST20170569
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.
Keywords
Monomeric GTP-Binding Proteins, Guanine Nucleotide Exchange Factors, Guanosine Diphosphate, Guanosine Triphosphate, Signal Transduction, Allosteric Site, Protein Structure, Secondary, Protein Binding, Mutation, Protein Domains
Identifiers
External DOI: https://doi.org/10.1042/BST20170569
This record's URL: https://www.repository.cam.ac.uk/handle/1810/283125
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