Crystal structure of a photoactivated deprotonated intermediate of rhodopsin
Crystal structure of a photoactivated deprotonated intermediate of rhodopsin
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DOI：
10.1073/pnas.0608022103
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发表时间：
2006-10-31
影响因子：
11.1
通讯作者：
Palczewski, Krzysztof
中科院分区：
文献类型：
--
作者：
Salom, David;Lodowski, David T.;Palczewski, Krzysztof
导致G蛋白偶联受体活化的变化尚未在结构水平上阐明。在这项工作中，我们报告的晶体结构的基态和光活化的去质子化的牛视紫红质的中间体在4.15埃的分辨率。在光活化状态下，连接发色团和Lys-296的席夫碱被去质子化，使人联想到G蛋白活化状态，即变视紫红质II。结构显示，伴随光活化的变化小于先前预测的metarhodopsin 11状态，并包括视紫红质的细胞质表面上的变化，可能使耦合到其同源G蛋白，transducin。此外，视紫红质形成了一个潜在的生理相关的二聚体界面，涉及螺旋1，11和8，当与先前的工作，牵连螺旋IV和V作为生理二聚体界面可能占一个界面的视紫红质的低聚结构的膜中看到的原子力显微镜。激活和寡聚化模型可能扩展到大多数其他G蛋白偶联受体。G
The changes that lead to activation of G protein-coupled receptors have not been elucidated at the structural level. In this work we report the crystal structures of both ground state and a photoactivated deprotonated intermediate of bovine rhodopsin at a resolution of 4.15 angstrom. in the photoactivated state, the Schiff base linking the chromophore and Lys-296 becomes deprotonated, reminiscent of the G protein-activating state, metarhodopsin II. The structures reveal that the changes that accompany photoactivation are smaller than previously predicted for the metarhodopsin 11 state and include changes on the cytoplasmic surface of rhodopsin that possibly enable the coupling to its cognate G protein, transducin. Furthermore, rhodopsin forms a potentially physiologically relevant dimer interface that involves helices 1, 11, and 8, and when taken with the prior work that implicates helices IV and V as the physiological dimer interface may account for one of the interfaces of the oligomeric structure of rhodopsin seen in the membrane by atomic force microscopy. The activation and oligomerization models likely extend to the majority of other G protein-coupled receptors. G