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Probing the activation-promoted structural rearrangements in preassembled receptor-G protein complexes.

Galés C, Van Durm JJ, Schaak S, Pontier S, Percherancier Y, Audet M, Paris H, Bouvier M

Department of Biochemistry and Groupe de Recherche Universitaire sur le Médicament, Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown station, Montreal, Quebec, Canada H3C 3J7.

Activation of heterotrimeric G proteins by their cognate seven transmembrane domain receptors is believed to involve conformational changes propagated from the receptor to the G proteins. However, the nature of these changes remains unknown. We monitored the conformational rearrangements at the interfaces between receptors and G proteins and between G protein subunits by measuring bioluminescence resonance energy transfer between probes inserted at multiple sites in receptor-G protein complexes. Using the data obtained for the alpha(2A)AR-G alpha(i1) beta1gamma2 complex and the available crystal structures of G alpha(i1) beta1gamma2, we propose a model wherein agonist binding induces conformational reorganization of a preexisting receptor-G protein complex, leading the G alpha-G betagamma interface to open but not dissociate. This conformational change may represent the movement required to allow nucleotide exit from the G alpha subunit, thus reflecting the initial activation event.

Nat. Struct. Mol. Biol. 2006;13(9):778-86.

Pubmed ID: 16906158

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