Structure-function of the G protein-coupled receptor superfamily.
Structure-function of the G protein-coupled receptor superfamily.
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DOI：
10.1146/annurev-pharmtox-032112-135923
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发表时间：
2013
影响因子：
12.5
通讯作者：
Stevens RC
中科院分区：
文献类型：
--
作者：
Katritch V;Cherezov V;Stevens RC
在过去几年中，G 蛋白偶联受体 (GPCR) 的晶体学经历了指数增长，导致 14 种不同受体的结构确定，仅 2012 年就确定了其中 7 种。包括密切相关的亚型同源模型，目前 GPCR 超家族的覆盖率约为 10%。现在已知肾上腺素能、视紫红质和腺苷受体系统的激动剂结合活性态结构，包括β2-肾上腺素能受体的受体-G-蛋白复合物的结构。核磁共振 (NMR) 和氢/氘交换质谱 (HDX-MS) 等生物化学和生物物理技术为不同功能状态之间配体依赖性动态平衡提供了补充见解。 1.8 A 腺苷 A2a 受体等高分辨率结构将受体描述为变构机器，不仅受配体控制，还受钠、脂质、胆固醇和水控制。这些丰富的数据有助于重新定义我们对 GPCR 如何识别如此多样化的配体阵列并跨细胞膜传输 30 埃信号的认识，同时还揭示了 GPCR 变构调节和偏向信号传导的结构基础。
During the past few years, crystallography of G protein-coupled receptors (GPCRs) has experienced exponential growth, resulting in structure determination of 14 distinct receptors, 7 of them in 2012 alone. Including closely related subtype homology models, this currently amounts to about 10% coverage of the GPCR superfamily. Agonist-bound active-state structures are now known for the adrenergic, rhodopsin, and adenosine receptor systems, including a structure of the receptor-G-protein complex for the β2-adrenergic receptor. Biochemical and biophysical techniques, such as nuclear magnetic resonance (NMR) and hydrogen/deuterium exchange-mass spectrometry (HDX-MS) are providing complementary insights on ligand-dependent dynamic equilibrium between different functional states. High resolution structures such as the 1.8 A adenosine A2a receptor are illistrating the receptor as allosteric machines, controlled not only by ligands, but by sodium, lipids, cholesterol, and water. This wealth of data is helping to redefine our knowledge of how GPCRs recognize such a diverse array of ligands and transmit signals 30 angstroms across the cell membrane, also shedding light on a structural basis of GPCR allosteric modulation and biased signaling.
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影响因子：
4.8
作者：
Ghanouni, P;Gryczynski, Z;Kobilka, BK
通讯作者：
Kobilka, BK
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作者：
Fredriksson, R;Schiöth, HB
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影响因子：
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通讯作者：
Marshall, Fiona H.