Cryo-EM structure of human rhodopsin bound to an inhibitory G protein.
Cryo-EM structure of human rhodopsin bound to an inhibitory G protein.
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DOI：
10.1038/s41586-018-0215-y
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发表时间：
2018-06
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;Kuybeda O;de Waal PW;Mukherjee S;Van Eps N;Dutka P;Zhou XE;Bartesaghi A;Erramilli S;Morizumi T;Gu X;Yin Y;Liu P;Jiang Y;Meng X;Zhao G;Melcher K;Ernst OP;Kossiakoff AA;Subramaniam S;Xu HE
G蛋白偶联受体是哺乳动物跨膜受体中最大的家族。它们通过与下游信号转导物偶联来介导许多细胞途径，包括异三聚体G蛋白Gs（刺激性）和Gi（抑制性）以及几种抑制蛋白。定义G蛋白偶联受体如何选择性地偶联到特定类型的G蛋白或抑制蛋白的结构机制仍然未知。在这里，使用冷冻电子显微镜，我们表明，激活的视紫红质和Gi之间的主要相互作用是由Gi α亚基的C-末端螺旋介导的，该螺旋楔入跨膜螺旋束的细胞质腔中，并直接接触视紫红质螺旋8的氨基末端。视紫红质的非活性、Gi结合和抑制蛋白结合形式与β2-肾上腺素能受体的非活性和Gs结合形式的结构比较为理解与活化的G蛋白偶联受体识别Gs、Gi和抑制蛋白相关的独特结构特征提供了基础。
G-protein-coupled receptors comprise the largest family of mammalian transmembrane receptors. They mediate numerous cellular pathways by coupling with downstream signalling transducers, including the hetrotrimeric G proteins Gs (stimulatory) and Gi (inhibitory) and several arrestin proteins. The structural mechanisms that define how G-protein-coupled receptors selectively couple to a specific type of G protein or arrestin remain unknown. Here, using cryo-electron microscopy, we show that the major interactions between activated rhodopsin and Gi are mediated by the C-terminal helix of the Gi α-subunit, which is wedged into the cytoplasmic cavity of the transmembrane helix bundle and directly contacts the amino terminus of helix 8 of rhodopsin. Structural comparisons of inactive, Gi-bound and arrestin-bound forms of rhodopsin with inactive and Gs-bound forms of the β2-adrenergic receptor provide a foundation to understand the unique structural signatures that are associated with the recognition of Gs, Gi and arrestin by activated G-protein-coupled receptors.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
64.8
作者：
Choe, Hui-Woog;Kim, Yong Ju;Ernst, Oliver P.
通讯作者：
Ernst, Oliver P.
影响因子：
11.4
作者：
GARCIA, PD;ONRUST, R;BOURNE, HR
通讯作者：
BOURNE, HR
影响因子：
64.8
作者：
Huang W;Manglik A;Venkatakrishnan AJ;Laeremans T;Feinberg EN;Sanborn AL;Kato HE;Livingston KE;Thorsen TS;Kling RC;Granier S;Gmeiner P;Husbands SM;Traynor JR;Weis WI;Steyaert J;Dror RO;Kobilka BK
通讯作者：
Kobilka BK
影响因子：
64.8
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
通讯作者：
Xu HE