Institut des Biomolécules Max Mousseron (IBMM, CNRS UMR5247), Faculté de Pharmacie, 15 avenue Charles Flahault, BP 14491, 34093 Montpellier Cedex 05, France.
FEBS Lett. 2013 Aug 19;587(16):2656-61. doi: 10.1016/j.febslet.2013.06.052. Epub 2013 Jul 10.
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.
G 蛋白偶联受体（GPCRs）在其激活过程中会发生较大的构象变化。从现有的 X 射线结构出发，我们使用正则模态分析（Normal Modes Analyses）研究了激动剂结合的β2-肾上腺素能受体在其分离的“非耦联”和 G 蛋白“耦联”构象中的集体运动。我们有趣地观察到，受体在蛋白-蛋白复合物中只能采用一种主要运动。这种运动对应于其细胞外和细胞内部分的反对称旋转，先前鉴定的高度保守脯氨酸残基起着关键作用。由于在对其他 7 种具有结构的 GPCR 进行 NMA 时也检索到了这种运动，因此强烈怀疑它具有重要的生物学作用，可能是与 G 蛋白耦联时 GPCR 的“激活模式”。
