Structural organization of a major neuronal G protein regulator, the RGS7-Gβ5-R7BP complex

Elife. 2018 Dec 12;7:e42150. doi: 10.7554/eLife.42150.


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.

Keywords: GPCR; cellular signaling; crystal structure; hydrogen-deuterium exchange mass-spectrometry; molecular biophysics; neurons; neuroscience; none; regulator of G-protein signaling; structural biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Crystallography, X-Ray
  • Deuterium Exchange Measurement
  • GTP-Binding Protein beta Subunits / chemistry*
  • GTP-Binding Protein beta Subunits / genetics
  • GTP-Binding Protein beta Subunits / metabolism
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mass Spectrometry
  • Molecular Dynamics Simulation*
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Neurons / metabolism*
  • Protein Conformation
  • Protein Multimerization
  • RGS Proteins / chemistry*
  • RGS Proteins / genetics
  • RGS Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Sf9 Cells
  • Spodoptera


  • Carrier Proteins
  • GNB5 protein, human
  • GTP-Binding Protein beta Subunits
  • Intracellular Signaling Peptides and Proteins
  • Multiprotein Complexes
  • RGS Proteins
  • RGS7 protein, human
  • RGS7BP protein, human
  • GTP-Binding Proteins