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

Auteur(s): Floquet N.

(Article) Publié: Febs Letters, vol. 587 p.2656-2661 (2013)

Ref HAL: hal-01107226_v1
PMID 23851072
DOI: 10.1016/j.febslet.2013.06.052

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.