Structure of the human secretin receptor coupled to an engineered heterotrimeric G protein
Structure of the human secretin receptor coupled to an engineered heterotrimeric G protein
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DOI：
10.1016/j.bbrc.2020.08.042
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发表时间：
2020-12-17
影响因子：
3.1
通讯作者：
Nureki, Osamu
中科院分区：
文献类型：
--
作者：
Fukuhara, Satoshi;Kobayashi, Kazuhiro;Nureki, Osamu
促胰液素是一种胃肠道激素，通过促胰液素受体（SECR）的激活发挥多种生理功能。SECR属于B类G蛋白偶联受体，并参与多种过程，如调节十二指肠内容物的pH、食物摄入和水稳态。在这里，我们报告了一个冷冻电镜结构的人SECR结合分泌素和工程Gs异源三聚体。该结构揭示了SECR的基本结构和分泌素结合模式。SECR和PAC1R跨膜结构域的结构比较显示，跨膜螺旋1和2在促胰液素识别中起着重要作用。此外，与PAC1R不同，SECR的胞外结构域垂直于TMD。这种比较揭示了这些受体的不同肽识别机制，它们属于同一亚组。我们的结构信息将促进临床应用的药物发现研究。(C)2020爱思唯尔公司All rights reserved.
Secretin is a gastrointestinal hormone that exerts multiple physiological functions via activation of the secretin receptor (SECR). SECR belongs to the class B G-protein-coupled receptors and is involved in various processes, such as regulation of the pH of the duodenal content, food intake, and water homeostasis. Here, we report a cryo-electron microscopy structure of human SECR bound to secretin and an engineered Gs heterotrimer. The structure revealed the basic architecture of SECR and the secretin binding mode. A structural comparison of the SECR and PAC1R transmembrane domains revealed that transmembrane helices 1 and 2 play a prominent role in secretin recognition. Moreover, the extracellular domain of SECR is perpendicular to the TMD, unlike that of PAC1R. This comparison revealed the diverged peptide recognition mechanisms of these receptors, which belong to the same subgroup. Our structural information will facilitate drug discovery research for clinical applications. (C) 2020 Elsevier Inc. All rights reserved.