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

Maxime Louet (1) , Esra Karakas (1) , Alexandre Perret (1) , David Perahia (2) , Jean Martinez (1) , Nicolas Floquet (1)

1 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
2 LBPA - Laboratoire de Biologie et de Pharmacologie Appliquée

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.

Mots clés: G-protein Coupled Receptor; G-protein heterotrimer complex; Normal Mode Analysis; Activation mechanism; Unique motion

Domaines: Chimie organique

Maxime Louet, Esra Karakas, Alexandre Perret, David Perahia, Jean Martinez, et al.. Conformational restriction of G-proteins Coupled Receptors (GPCRs) upon complexation to G-proteins: A putative activation mode of GPCRs?. FEBS Letters, 2013, 587 (16), pp.2656-2661. ⟨10.1016/j.febslet.2013.06.052⟩. ⟨hal-01107226⟩