Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.
Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.
复制标题
DOI：
10.1038/nature14656
复制
发表时间：
2015-07-30
期刊：
影响因子：
64.8
通讯作者：
Xu HE
中科院分区：
文献类型：
--
作者：
Kang Y;Zhou XE;Gao X;He Y;Liu W;Ishchenko A;Barty A;White TA;Yefanov O;Han GW;Xu Q;de Waal PW;Ke J;Tan MH;Zhang C;Moeller A;West GM;Pascal BD;Van Eps N;Caro LN;Vishnivetskiy SA;Lee RJ;Suino-Powell KM;Gu X;Pal K;Ma J;Zhi X;Boutet S;Williams GJ;Messerschmidt M;Gati C;Zatsepin NA;Wang D;James D;Basu S;Roy-Chowdhury S;Conrad CE;Coe J;Liu H;Lisova S;Kupitz C;Grotjohann I;Fromme R;Jiang Y;Tan M;Yang H;Li J;Wang M;Zheng Z;Li D;Howe N;Zhao Y;Standfuss J;Diederichs K;Dong Y;Potter CS;Carragher B;Caffrey M;Jiang H;Chapman HN;Spence JC;Fromme P;Weierstall U;Ernst OP;Katritch V;Gurevich VV;Griffin PR;Hubbell WL;Stevens RC;Cherezov V;Melcher K;Xu HE
G 蛋白偶联受体 (GPCR) 主要通过 G 蛋白或抑制蛋白发出信号。 Arrestin 与 GPCR 结合可阻断 G 蛋白相互作用，并将信号转导至许多不依赖于 G 蛋白的途径。在这里，我们报告了人视紫红质的组成型活性形式与小鼠视觉视紫红质的预激活形式结合的晶体结构，这是通过连续飞秒 X 射线激光晶体学测定的。结合大量的生化和诱变数据，该结构揭示了视紫红质-抑制蛋白组装体的整体架构，其中视紫红质使用不同的结构元件，包括 TM7 和 Helix 8 来招募抑制蛋白。相应地，视紫红质抑制蛋白采用预激活构象，N 结构域和 C 结构域之间旋转约 20°，这在视紫红质抑制蛋白中打开一个裂缝，以容纳由视紫红质第二个细胞内环形成的短螺旋。该结构为理解 GPCR 介导的抑制蛋白偏向信号传导提供了基础，并展示了 X 射线激光推进结构生物学前沿的力量。
G protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signaling to numerous G protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly, in which rhodopsin uses distinct structural elements, including TM7 and Helix 8 to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ~20° rotation between the N- and C- domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signaling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology.