Structure of the human secretin receptor coupled to an engineered heterotrimeric G protein

被引：17

作者：

Fukuhara, Satoshi ^{[1
,2
]}

Kobayashi, Kazuhiro ^{[1
]}

Kusakizako, Tsukasa ^{[1
]}

Iida, Wataru ^{[1
]}

Kato, Masahiko ^{[1
]}

Shihoya, Wataru ^{[1
]}

Nureki, Osamu ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan

[2] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Family Med, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138519, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2020年 / 533卷 / 04期

关键词：

Cryo-EM; GPCR; Ligand recognition; CRYO-EM STRUCTURE; MICE;

D O I：

10.1016/j.bbrc.2020.08.042

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：861 / 866

页数：6

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