Integrating energy calculations with functional assays to decipher the specificity of G protein-RGS protein interactions.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Kosloff, M; Travis, AM; Bosch, DE; Siderovski, DP; Arshavsky, VY
Published Date
- June 19, 2011
Published In
Volume / Issue
- 18 / 7
Start / End Page
- 846 - 853
PubMed ID
- 21685921
Pubmed Central ID
- PMC3130846
Electronic International Standard Serial Number (EISSN)
- 1545-9985
Digital Object Identifier (DOI)
- 10.1038/nsmb.2068
Language
- eng
Conference Location
- United States