Sequential Conformational Rearrangements Dictate the Dynamics of Class C GPCR Activation

Sci. Signal., 20 November 2012
Vol. 5, Issue 251, p. pe51
DOI: 10.1126/scisignal.2003503

Sequential Conformational Rearrangements Dictate the Dynamics of Class C GPCR Activation

  1. J. Robert Lane and
  2. Meritxell Canals*
  1. Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, and Department of Pharmacology, Monash University, Parkville, Victoria 3052, Australia.
  1. *Corresponding author. E-mail: meri.canals{at}monash.edu

Abstract

Heterotrimeric GTP-binding protein (G protein)–coupled receptors (GPCRs) are the largest family of cell surface receptors; they allow cells to respond to a wide range of endogenous and environmental signals. Class C GPCRs represent a discrete group within the GPCR family, with distinct structural characteristics. Receptors belonging to this class—such as γ-aminobutyric acid type B (GABAB) receptors or metabotropic glutamate receptors (mGluRs)—form constitutive dimers. However, the conformational changes within such a dimeric receptor that are associated with agonist activation are still not well understood. A study by Hlavackova et al. investigates the role of dimer formation in mGluR1 activation. Using fluorescence resonance energy transfer approaches to assess inter- and intrasubunit conformational changes, the authors present an elegant study that sheds light on the kinetics of domain rearrangements in a class C GPCR upon ligand binding

Citation:

J. R. Lane and M. Canals, Sequential Conformational Rearrangements Dictate the Dynamics of Class C GPCR Activation. Sci. Signal. 5, pe51 (2012).
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