Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Feb;11(2):134-40.
doi: 10.1038/nchembio.1711. Epub 2014 Dec 15.

Major ligand-induced rearrangement of the heptahelical domain interface in a GPCR dimer

Li Xue  1 , Xavier Rovira  2 , Pauline Scholler  2 , Han Zhao  3 , Jianfeng Liu  3 , Jean-Philippe Pin  2 , Philippe Rondard  2
Affiliations

Major ligand-induced rearrangement of the heptahelical domain interface in a GPCR dimer

Li Xue et al. Nat Chem Biol. 2015 Feb.

Abstract

G protein-coupled receptors (GPCRs) are major players in cell communication. Although they form functional monomers, increasing evidence indicates that GPCR dimerization has a critical role in cooperative phenomena that are important for cell signal integration. However, the structural bases of these phenomena remain elusive. Here, using well-characterized receptor dimers, the metabotropic glutamate receptors (mGluRs), we show that structural changes at the dimer interface are linked to receptor activation. We demonstrate that the main dimer interface is formed by transmembrane α helix 4 (TM4) and TM5 in the inactive state and by TM6 in the active state. This major change in the dimer interface is required for receptor activity because locking the TM4-TM5 interface prevents activation by agonist, whereas locking the TM6 interface leads to a constitutively active receptor. These data provide important information on the activation mechanism of mGluRs and improve our understanding of the structural basis of the negative cooperativity observed in these GPCR dimers.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Curr Opin Cell Biol. 2014 Apr;27:78-86 - PubMed
    1. Science. 2014 Apr 4;344(6179):58-64 - PubMed
    1. Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2660-5 - PubMed
    1. Curr Opin Cell Biol. 2014 Apr;27:136-43 - PubMed
    1. Nature. 2011 Jul 19;477(7366):549-55 - PubMed

Publication types

MeSH terms

LinkOut - more resources

  NODES
twitter 2