Nature Structural & Molecular Biology
- 13, 778 - 786 (2006)
Published online: 13 August 2006; | doi:10.1038/nsmb1134
Probing the activation-promoted structural rearrangements in preassembled receptor–G protein complexesCéline Galés1, Joost J J Van Durm2, Stéphane Schaak3, Stéphanie Pontier1, Yann Percherancier1, Martin Audet1, Hervé Paris3 & Michel Bouvier11
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. 2
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Campus Erasme, C.P. 602, route de Lennik 808, 1070 Brussels, Belgium. 3
INSERM U388, Institut Louis Bugnard, CHU Rangueil, BP 84225, Toulouse 31432 Cedex 4, France.
Correspondence should be addressed to Michel Bouvier michel.bouvier@umontreal.ca 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  2AAR–Gi1 1 2 complex and the available crystal structures of Gi112, we propose a model wherein agonist binding induces conformational reorganization of a preexisting receptor–G protein complex, leading the G-G interface to open but not dissociate. This conformational change may represent the movement required to allow nucleotide exit from the G subunit, thus reflecting the initial activation event.
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