Journal article
Integrating energy calculations with functional assays to decipher the specificity of G protein-RGS protein interactions
Nature structural & molecular biology, Vol.18(7), pp.846-853
07/2011
DOI: 10.1038/nsmb.2068
PMID: 21685921
Abstract
The diverse Regulator of G protein Signaling (RGS) family sets the timing of G protein signaling. To understand how the structure of RGS proteins determines their common ability to inactivate G proteins and their selective G protein recognition, we combined structure-based energy calculations with biochemical measurements of RGS activity. We found a previously unidentified group of variable 'Modulatory' residues that reside at the periphery of the RGS domain-G protein interface and fine-tune G protein recognition. Mutations of Modulatory residues in high-activity RGS proteins impaired RGS function, whereas redesign of low-activity RGS proteins in critical Modulatory positions yielded complete gain of function. Therefore, RGS proteins combine a conserved core interface with peripheral Modulatory residues to selectively optimize G protein recognition and inactivation. Finally, we show that our approach can be extended to analyze interaction specificity across other large protein families.
Details
- Title: Subtitle
- Integrating energy calculations with functional assays to decipher the specificity of G protein-RGS protein interactions
- Creators
- Vadim Y Arshavsky - Duke UniversityMickey Kosloff - Duke UniversityAmanda M Travis - Duke UniversityDustin E Bosch - University of North Carolina at Chapel HillDavid P Siderovski - University of North Carolina at Chapel Hill
- Resource Type
- Journal article
- Publication Details
- Nature structural & molecular biology, Vol.18(7), pp.846-853
- DOI
- 10.1038/nsmb.2068
- PMID
- 21685921
- NLM abbreviation
- Nat Struct Mol Biol
- ISSN
- 1545-9993
- eISSN
- 1545-9985
- Language
- English
- Date published
- 07/2011
- Academic Unit
- Pathology
- Record Identifier
- 9984200019102771
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