Structural basis for motilin and erythromycin recognition by motilin receptor

doi:10.1126/sciadv.ade9020

	Structural basis for motilin and erythromycin recognition by motilin receptor
	You, Chongzhao 1,2; Zhang, Yumu3 ; Xu, Youwei 1; Xu, Peiyu 1,6; Li, Zhen 4; Li, Huadong3 ; Huang, Sijie 1,7; Chen, Zecai 1,2; Li, Jingru 4; Xu, Eric 1,2,3,4,5; Jiang, Yi3,5
	2023-03
发表期刊	SCIENCE ADVANCES (IF:11.7[JCR-2023],13.7[5-Year])
ISSN	2375-2548
EISSN	2375-2548
卷号	9 期号:11
发表状态	已发表
DOI	10.1126/sciadv.ade9020
摘要	Motilin is an endogenous peptide hormone almost exclusively expressed in the human gastrointestinal (GI) tract. It activates the motilin receptor (MTLR), a class A G protein–coupled receptor (GPCR), and stimulates GI motility. To our knowledge, MTLR is the first GPCR reported to be activated by macrolide antibiotics, such as erythromycin. It has attracted extensive attention as a potential drug target for GI disorders. We report two structures of Gq-coupled human MTLR bound to motilin and erythromycin. Our structures reveal the recognition mechanism of both ligands and explain the specificity of motilin and ghrelin, a related gut peptide hormone, for their respective receptors. These structures also provide the basis for understanding the different recognition modes of erythromycin by MTLR and ribosome. These findings provide a framework for understanding the physiological regulation of MTLR and guiding drug design targeting MTLR for the treatment of GI motility disorders. Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.
关键词	Hormones Peptides Class A G protein coupled receptors Gastrointestinal disorders Gastrointestinal motility Gastrointestinal tract Macrolide antibiotics Peptide hormones Potential drug targets Recognition mechanism Structural basis
URL	查看原文
收录类别	SCI ; EI
语种	英语
资助项目	National Natural Science Foundation[
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000968083500004
出版者	American Association for the Advancement of Science
EI入藏号	20231513875965
EI主题词	Antibiotics
EI分类号	461.2 Biological Materials and Tissue Engineering ; 461.6 Medicine and Pharmacology ; 461.9 Biology
原始文献类型	Journal article (JA)
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/292218
专题	生命科学与技术学院_博士生生命科学与技术学院
通讯作者	Xu, Eric; Jiang, Yi
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol ogy, Shanghai 201210, Peoples R China 4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China 5.Lingang Lab, Shanghai 200031, Peoples R China 6.MIT, McGovern Inst Brain Res, Cambridge, MA USA 7.Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA USA
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	You, Chongzhao,Zhang, Yumu,Xu, Youwei,et al. Structural basis for motilin and erythromycin recognition by motilin receptor[J]. SCIENCE ADVANCES,2023,9(11).
APA	You, Chongzhao.,Zhang, Yumu.,Xu, Youwei.,Xu, Peiyu.,Li, Zhen.,...&Jiang, Yi.(2023).Structural basis for motilin and erythromycin recognition by motilin receptor.SCIENCE ADVANCES,9(11).
MLA	You, Chongzhao,et al."Structural basis for motilin and erythromycin recognition by motilin receptor".SCIENCE ADVANCES 9.11(2023).