Structural organization of a major neuronal G protein regulator, the RGS7-Gβ5-R7BP complex
- The Scripps Research Institute, United States
Abstract
Signaling by the G protein Coupled Receptors (GPCRs) plays fundamental role in a vast number of essential physiological functions. Precise control of GPCR signaling requires action of Regulators of G protein Signaling (RGS) proteins that deactivate heterotrimeric G proteins. RGS proteins are elaborately regulated and comprise multiple domains and subunits, yet structural organization of these assemblies is poorly understood. Here we report a crystal structure and dynamics analyses of the multisubunit complex of RGS7, a major regulator of neuronal signaling with key roles in controlling a number of drug target GPCRs and links to neuropsychiatric disease, metabolism, and cancer. The crystal structure in combination with molecular dynamics and mass spectrometry analyses reveals unique organizational features of the complex and long-range conformational changes imposed by its constituent subunits during allosteric modulation. Notably, several intermolecular interfaces in the complex work in synergy to provide coordinated modulation of this key GPCR regulator.
Data availability
Coordinate and structure factor have been deposited in the protein data bank with accession codes 6N9G. Raw HDX data are deposited at https://doi.org/10.6084/m9.figshare.7316462.v2
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Mass Spec Raw File Datafigshare, doi.org/10.6084/m9.figshare.7316462.v2.
Article and author information
Author details
Kirill A Martemyanov
Funding
National Institute on Drug Abuse (DA036596)
- Kirill A Martemyanov
National Eye Institute (EY018139)
- Kirill A Martemyanov
National Institute on Drug Abuse (DA042746)
- Kirill A Martemyanov
National Institute of General Medical Sciences (GM114420)
- Douglas J Kojetin
National Institute of Diabetes and Digestive and Kidney Diseases (DK105825)
- Patrick R Griffin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- José D Faraldo-Gómez, National Heart, Lung and Blood Institute, National Institutes of Health, United States
Version history
- Received: September 18, 2018
- Accepted: December 12, 2018
- Accepted Manuscript published: December 12, 2018 (version 1)
- Version of Record published: December 28, 2018 (version 2)
- Version of Record updated: March 2, 2020 (version 3)
Copyright
© 2018, Patil et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Structural organization of a major neuronal G protein regulator, the RGS7-Gβ5-R7BP complex
eLife 7:e42150.
https://doi.org/10.7554/eLife.42150
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