Crystal structure of opsin in its G-protein-interacting conformation
Crystal structure of opsin in its G-protein-interacting conformation
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DOI：
10.1038/nature07330
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发表时间：
2008-09-25
期刊：
影响因子：
64.8
通讯作者：
Ernst, Oliver P.
中科院分区：
文献类型：
--
作者：
Scheerer, Patrick;Park, Jung Hee;Ernst, Oliver P.
视蛋白是G-蛋白偶联受体视紫红质的无配体形式，在低pH下呈现构象上不同的活性G-蛋白结合状态，称为Ops*.来自异源三聚体G蛋白主要结合位点的合成肽-α亚基（G α CT）的羧基末端-稳定Ops*。在这里，我们提出了牛Ops* - G α CT肽复合物的3.2埃晶体结构。G α CT与视蛋白中的一个位点结合，该位点通过跨膜螺旋（TM）6的向外倾斜、TM 5和TM 6的配对以及重构的TM 7-螺旋8扭结而打开。沿着TM 5和TM 6内表面的接触诱导G α CT中的α螺旋构象，其具有C末端反向转弯。主链上的羰基反过来构成了氢键网络的中心，它连接了含有保守的E（D）RY和NPxxY（x）（5，6）F基序的两个受体区域.基于Ops* - G α CT结构和已知的G α构象变化，我们讨论了从受体到G蛋白核苷酸结合位点的信号传递。
Opsin, the ligand- free form of the G- protein- coupled receptor rhodopsin, at low pH adopts a conformationally distinct, active G- protein- binding state known as Ops*. A synthetic peptide derived from the main binding site of the heterotrimeric G protein - the carboxy terminus of the alpha-subunit (G alpha CT) - stabilizes Ops*. Here we present the 3.2 angstrom crystal structure of the bovine Ops* - G alpha CT peptide complex. G alpha CT binds to a site in opsin that is opened by an outward tilt of transmembrane helix ( TM) 6, a pairing of TM5 and TM6, and a restructured TM7 - helix 8 kink. Contacts along the inner surface of TM5 and TM6 induce an alpha- helical conformation in G alpha CT with a C- terminal reverse turn. Main- chain carbonyl groups in the reverse turn constitute the centre of a hydrogen- bonded network, which links the two receptor regions containing the conserved E( D) RY and NPxxY(x)(5,6)F motifs. On the basis of the Ops* - G alpha CT structure and known conformational changes in G alpha, we discuss signal transfer from the receptor to the G protein nucleotide- binding site.