Conformational restriction of G-proteins Coupled Receptors (GPCRs) upon complexation to G-proteins: a putative activation mode of GPCRs?

FEBS Lett. 2013 Aug 19;587(16):2656-61. doi: 10.1016/j.febslet.2013.06.052. Epub 2013 Jul 10.


GPCRs undergo large conformational changes during their activation. Starting from existing X-ray structures, we used Normal Modes Analyses to study the collective motions of the agonist-bound β2-adrenergic receptor both in its isolated "uncoupled" and G-protein "coupled" conformations. We interestingly observed that the receptor was able to adopt only one major motion in the protein:protein complex. This motion corresponded to an anti-symmetric rotation of both its extra- and intra-cellular parts, with a key role of previously identified highly conserved proline residues. Because this motion was also retrieved when performing NMA on 7 other GPCRs which structures were available, it is strongly suspected to possess a significant biological role, possibly being the "activation mode" of a GPCR when coupled to G-proteins.

Keywords: Activation mechanism; G-protein Coupled Receptor; G-protein heterotrimer complex; MRMS; Mass-weighted Root Mean Square; Normal Mode Analysis; Unique motion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • GTP-Binding Proteins / chemistry*
  • Humans
  • Lipid Bilayers / chemistry
  • Models, Molecular
  • Phospholipids / chemistry
  • Protein Binding
  • Protein Conformation
  • Receptors, Adrenergic, beta-2 / chemistry
  • Receptors, G-Protein-Coupled / chemistry*


  • Lipid Bilayers
  • Phospholipids
  • Receptors, Adrenergic, beta-2
  • Receptors, G-Protein-Coupled
  • GTP-Binding Proteins