Galés Céline, Van Durm Joost J J, Schaak Stéphane, Pontier Stéphanie, Percherancier Yann, Audet Martin, Paris Hervé, Bouvier Michel
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.
Nat Struct Mol Biol. 2006 Sep;13(9):778-86. doi: 10.1038/nsmb1134. Epub 2006 Aug 13.
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.
异源三聚体G蛋白被其相应的七跨膜结构域受体激活，据信这涉及从受体传播到G蛋白的构象变化。然而，这些变化的本质仍然未知。我们通过测量插入受体 - G蛋白复合物多个位点的探针之间的生物发光共振能量转移，监测受体与G蛋白之间以及G蛋白亚基之间界面处的构象重排。利用α(2A)肾上腺素能受体 - Gα(i1)β1γ2复合物获得的数据以及Gα(i1)β1γ2的现有晶体结构，我们提出了一个模型，其中激动剂结合诱导预先存在的受体 - G蛋白复合物的构象重组，导致Gα - Gβγ界面打开但不解离。这种构象变化可能代表了允许核苷酸从Gα亚基中排出所需的运动，从而反映了初始激活事件。
