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Molecular Basis for Hormone Recognition and Activation of Corticotropin-Releasing Factor Receptors

文献类型：期刊论文

作者Ma, Shanshan1,2; Shen, Qingya3,4; Zhao, Li-Hua1; Mao, Chunyou3,4; Zhou, X. Edward5; Shen, Dan-Dan3,4; de Waal, Parker W.5; Bi, Peng3,4; Li, Chuntao3,4; Jiang, Yi1
刊名MOLECULAR CELL
出版日期2020-02-06
卷号77期号:3页码:669-+
ISSN号1097-2765
DOI10.1016/j.molcel.2020.01.013
通讯作者Zhao, Li-Hua(zhaolihuawendy@simm.ac.cn) ; Zhang, Yan(zhang_yan@zju.edu.cn) ; Xu, H. Eric(eric.xu@simm.ac.cn)
英文摘要Corticotropin-releasing factor (CRF) and the three related peptides urocortins 1-3 (UCN1-UCN3) are endocrine hormones that control the stress responses by activating CRF1R and CRF2R, two members of class B G-protein-coupled receptors (GPCRs). Here, we present two cryoelectron microscopy (cryo-EM) structures of UCN1-bound CRF1R and CRF2R with the stimulatory G protein. In both structures, UCN1 adopts a single straight helix with its N terminus dipped into the receptor transmembrane bundle. Although the peptide-binding residues in CRF1R and CRF2R are different from other members of class B GPCRs, the residues involved in receptor activation and G protein coupling are conserved. In addition, both structures reveal bound cholesterol molecules to the receptor transmembrane helices. Our structures define the basis of ligand-binding specificity in the CRF receptor-hormone system, establish a common mechanism of class B GPCR activation and G protein coupling, and provide a paradigm for studying membrane protein-lipid interactions for class B GPCRs.
WOS关键词CRYO-EM STRUCTURE ; G-PROTEIN ; UROCORTIN-II ; LIPID RAFTS ; CRF ; STRESS ; PITUITARY ; PEPTIDE ; BINDING ; FAMILY
资助项目Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; Shanghai Science and Technology Development Fund[18ZR1447800] ; Young Innovator Association of CAS[2018325] ; Fudan-SIMM Joint Research Fund[FU-SIMM-20174003] ; SA-SIBS Scholarship Program ; Jay and Betty Van Andel Foundation ; National Institutes of Health[GM127710] ; Zhejiang Province Science Fund for Distinguished Young Scholars[LR19H310001] ; National Natural Science Foundation[31770796] ; National Science and Technology Major Project[2018ZX09711002]
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
出版者CELL PRESS
WOS记录号WOS:000512932100019
源URL[http://119.78.100.183/handle/2S10ELR8/281458]  
专题中国科学院上海药物研究所
通讯作者Zhao, Li-Hua; Zhang, Yan; Xu, H. Eric
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Biophys, Sch Med, Hangzhou 310058, Peoples R China
4.Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Pathol, Sch Med, Hangzhou 310058, Peoples R China
5.Van Andel Res Inst, Ctr Canc & Cell Biol, Program Struct Biol, Grand Rapids, MI USA
6.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
7.Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol, Parkville, Vic 3052, Australia
8.Monash Univ, Monash Inst Pharmaceut Sci, Dept Pharmacol, Parkville, Vic 3052, Australia
推荐引用方式
GB/T 7714		 Ma, Shanshan,Shen, Qingya,Zhao, Li-Hua,et al. Molecular Basis for Hormone Recognition and Activation of Corticotropin-Releasing Factor Receptors[J]. MOLECULAR CELL,2020,77(3):669-+.
APA Ma, Shanshan.,Shen, Qingya.,Zhao, Li-Hua.,Mao, Chunyou.,Zhou, X. Edward.,...&Xu, H. Eric.(2020).Molecular Basis for Hormone Recognition and Activation of Corticotropin-Releasing Factor Receptors.MOLECULAR CELL,77(3),669-+.
MLA Ma, Shanshan,et al."Molecular Basis for Hormone Recognition and Activation of Corticotropin-Releasing Factor Receptors".MOLECULAR CELL 77.3(2020):669-+.

入库方式： OAI收割

来源：上海药物研究所

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