title: Conformational restriction of G-proteins Coupled Receptors (GPCRs) upon complexation to G-proteins: a putative activation mode of GPCRs?
abstract: 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.
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM, CNRS UMR5247), Faculté de Pharmacie, 15 avenue Charles Flahault, BP 14491, 34093 Montpellier Cedex 05, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Louet
authors.forename: Esra
authors.initials: E
authors.lastname: Karakas
authors.forename: Alexandre
authors.initials: A
authors.lastname: Perret
authors.forename: David
authors.initials: D
authors.lastname: Perahia
authors.forename: Jean
authors.initials: J
authors.lastname: Martinez
authors.forename: Nicolas
authors.initials: N
authors.lastname: Floquet
mesh_terms: D019204:GTP-Binding Proteins / Q000737:chemistry*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008958:Models, Molecular; D010743:Phospholipids / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D010743:Phospholipids; D018343:Receptors, Adrenergic, beta-2; D043562:Receptors, G-Protein-Coupled; D019204:GTP-Binding Proteins
keywords: Activation mechanism; G-protein Coupled Receptor; G-protein heterotrimer complex; MRMS; Mass-weighted Root Mean Square; Normal Mode Analysis; Unique motion