Park Jung Hee, Scheerer Patrick, Hofmann Klaus Peter, Choe Hui-Woog, Ernst Oliver Peter
Institut für Medizinische Physik und Biophysik (CC2), Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
Nature. 2008 Jul 10;454(7201):183-7. doi: 10.1038/nature07063. Epub 2008 Jun 18.
In the G-protein-coupled receptor (GPCR) rhodopsin, the inactivating ligand 11-cis-retinal is bound in the seven-transmembrane helix (TM) bundle and is cis/trans isomerized by light to form active metarhodopsin II. With metarhodopsin II decay, all-trans-retinal is released, and opsin is reloaded with new 11-cis-retinal. Here we present the crystal structure of ligand-free native opsin from bovine retinal rod cells at 2.9 ångström (A) resolution. Compared to rhodopsin, opsin shows prominent structural changes in the conserved E(D)RY and NPxxY(x)(5,6)F regions and in TM5-TM7. At the cytoplasmic side, TM6 is tilted outwards by 6-7 A, whereas the helix structure of TM5 is more elongated and close to TM6. These structural changes, some of which were attributed to an active GPCR state, reorganize the empty retinal-binding pocket to disclose two openings that may serve the entry and exit of retinal. The opsin structure sheds new light on ligand binding to GPCRs and on GPCR activation.
在G蛋白偶联受体（GPCR）视紫红质中，失活配体11-顺式视黄醛结合在七跨膜螺旋（TM）束中，并通过光进行顺/反异构化形成活性视紫红质II。随着视紫红质II的衰变，全反式视黄醛被释放，视蛋白重新装载新的11-顺式视黄醛。在这里，我们展示了来自牛视网膜杆细胞的无配体天然视蛋白在2.9埃（Å）分辨率下的晶体结构。与视紫红质相比，视蛋白在保守的E（D）RY和NPxxY（x）（5,6）F区域以及TM5-TM7中显示出显著的结构变化。在细胞质侧，TM6向外倾斜6-7 Å，而TM5的螺旋结构更加细长且靠近TM6。这些结构变化，其中一些归因于活性GPCR状态，重新组织了空的视黄醛结合口袋，以揭示两个可能用于视黄醛进出的开口。视蛋白结构为配体与GPCR的结合以及GPCR激活提供了新的见解。
