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

クライオ電子顕微鏡を用いた単粒子解析法により、セクレチン、セレクチン受容体、３量体Gタンパク質の複合体の構造を明らかにした。
セクレチンは重炭酸イオンの分泌を促進して胃での消化物を腸で中和するのに機能し、また胃酸の分泌を抑える働きをもつ。
セクレチンとセレクチン受容体の詳細な結合メカニズムの解明は、消化器疾患の治療薬の開発に役立つ。

Abstract

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.

分解能

2.9Å

Citation