Abstract
The structural basis for the GTPase-accelerating activity of regulators of G protein signaling (RGS) proteins, as well as the mechanistic basis for their specificity in interacting with the heterotrimeric (αβγ) G proteins they inactivate, is not sufficiently understood at the family level. Here, we used biochemical assays to compare RGS domains across the RGS family and map those individual residues that favorably contribute to GTPase-accelerating activity, and those residues responsible for attenuating RGS domain interactions with Gα subunits. We show that conserved interactions of RGS residues with both the Gα switch I and II regions are crucial for RGS activity, while the reciprocal effects of “modulatory” and “disruptor” residues selectively modulate RGS activity. Our results quantify how specific interactions between RGS domains and Gα subunits are set by a balance between favorable RGS residue interactions with particular Gα switch regions, and unfavorable interactions with the Gα helical domain.
Original language | English |
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Pages (from-to) | 6305-6318 |
Number of pages | 14 |
Journal | Cellular and Molecular Life Sciences |
Volume | 78 |
Issue number | 17-18 |
DOIs | |
State | Published - Sep 2021 |
Bibliographical note
Publisher Copyright:© 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Keywords
- GTPases
- Protein structure
- Protein–protein interactions
- Signal transduction
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Pharmacology
- Cellular and Molecular Neuroscience
- Cell Biology