Probing the activation-promoted structural rearrangements in preassembled receptor-G protein complexes
Probing the activation-promoted structural rearrangements in preassembled receptor-G protein complexes
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DOI：
10.1038/nsmb1134
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发表时间：
2006-09-01
影响因子：
16.8
通讯作者：
Bouvier, Michel
中科院分区：
文献类型：
--
作者：
Gales, Celine;Van Durm, Joost J. J.;Bouvier, Michel
异源三聚体G蛋白通过其同源七跨膜结构域受体的活化被认为涉及从受体传播到G蛋白的构象变化。然而，这些变化的性质仍然未知。我们监测受体和G蛋白之间的接口和G蛋白亚基之间的构象重排，通过测量插入在多个位点的受体-G蛋白复合物的探针之间的生物发光共振能量转移。利用从α（2A）AR-G α（i1）β（1）γ（2）复合物获得的数据和G α（i1）β（1）γ（2）的可用晶体结构，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G α-G β γ界面打开但不解离。这种构象变化可能代表允许核苷酸从G α亚基离开所需的运动，从而反映了初始激活事件。
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)beta(1)gamma(2) complex and the available crystal structures of G alpha(i1)beta(1)gamma(2), we propose a model wherein agonist binding induces conformational reorganization of a preexisting receptor-G protein complex, leading the G alpha-G beta gamma 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.