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Toward a Structural Understanding of Class B GPCR Peptide Binding and Activation

文献类型：期刊论文

作者Liang, Yi-Lynn1,2; Belousoff, Matthew J.1,2; Zhao, Peishen1,2; Koole, Cassandra1,2; Fletcher, Madeleine M.1,2; Truong, Tin T.1,2; Julita, Villy1,2; Christopoulos, George1,2; Xu, H. Eric3,4; Zhang, Yan5,6
刊名MOLECULAR CELL
出版日期2020-02-06
卷号77期号:3页码:656-+
ISSN号1097-2765
DOI10.1016/j.molcel.2020.01.012
通讯作者Danev, Radostin(rado@m.u-tokyo.ac.jp) ; Sexton, Patrick M.(patrick.sexton@monash.edu) ; Wootten, Denise(denise.wootten@monash.edu)
英文摘要Class B G protein-coupled receptors (GPCRs) are important therapeutic targets for major diseases. Here, we present structures of peptide and Gsbound pituitary adenylate cyclase-activating peptide, PAC1 receptor, and corticotropin-releasing factor (CRF), (CRF1) receptor. Together with recently solved structures, these provide coverage of the major class B GPCR subfamilies. Diverse orientations of the extracellular domain to the receptor core in different receptors are at least partially dependent on evolutionary conservation in the structure and nature of peptide interactions. Differences in peptide interactions to the receptor core also influence the interlinked TM2-TM1-TM6/ECL3/TM7 domain, and this is likely important in their diverse signaling. However, common conformational reorganization of ECL2, linked to reorganization of ICL2, modulates G protein contacts. Comparison between receptors reveals ICL2 as a key domain forming dynamic G protein interactions in a receptor- and ligand-specific manner. This work advances our understanding of class B GPCR activation and Gs coupling.
WOS关键词CRYO-EM STRUCTURE ; CORTICOTROPIN-RELEASING-FACTOR ; GLP-1 RECEPTOR ; DETERMINANTS ; RECOGNITION ; DYNAMICS ; COMPLEX ; SURFACE
资助项目Monash University Ramaciotti Centre for Cryo-Electron Microscopy ; National Health and Medical Research Council of Australia (NHMRC)[1120919] ; National Health and Medical Research Council of Australia (NHMRC)[1159006] ; NHMRC[1150083] ; Japan Society for the Promotion of Science (JSPS) KAKENHI grant[18H06043] ; Japan Science and Technology Agency (JST) PRESTO grant[18069571] ; Monash MASSIVE high-performance computing facility
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
WOS记录号WOS:000512932100018
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/281361]  
专题中国科学院上海药物研究所
通讯作者Danev, Radostin; Sexton, Patrick M.; Wootten, Denise
作者单位1.Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol, Parkville, Vic 3052, Australia
2.Monash Univ, Monash Inst Pharmaceut Sci, Dept Pharmacol, Parkville, Vic 3052, Australia
3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
4.Van Andel Res Inst, Ctr Canc & Cell Biol, Innovat & Integrat Program, Grand Rapids, MI USA
5.Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Biophys, Hangzhou 310058, Peoples R China
6.Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Pathol, Hangzhou 310058, Peoples R China
7.Max Planck Inst Biochem, Dept Mol Struct Biol, D-82152 Martinsried, Germany
8.Univ Tokyo, Grad Sch Med, Bunkyo Ku, S402,7-3-1 Hongo, Tokyo 1130033, Japan
9.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
10.Novartis Pharma AG, Novartis Inst Biomed Res, CH-4002 Basel, Switzerland
推荐引用方式
GB/T 7714		 Liang, Yi-Lynn,Belousoff, Matthew J.,Zhao, Peishen,et al. Toward a Structural Understanding of Class B GPCR Peptide Binding and Activation[J]. MOLECULAR CELL,2020,77(3):656-+.
APA Liang, Yi-Lynn.,Belousoff, Matthew J..,Zhao, Peishen.,Koole, Cassandra.,Fletcher, Madeleine M..,...&Wootten, Denise.(2020).Toward a Structural Understanding of Class B GPCR Peptide Binding and Activation.MOLECULAR CELL,77(3),656-+.
MLA Liang, Yi-Lynn,et al."Toward a Structural Understanding of Class B GPCR Peptide Binding and Activation".MOLECULAR CELL 77.3(2020):656-+.

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来源：上海药物研究所

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