Structure and dynamics of the M3 muscarinic acetylcholine receptor
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kruse, Andrew C. | - |
dc.contributor.author | Hu, Jianxin | - |
dc.contributor.author | Pan, Albert C. | - |
dc.contributor.author | Arlow, Daniel H. | - |
dc.contributor.author | Rosenbaum, Daniel M. | - |
dc.contributor.author | Rosemond, Erica | - |
dc.contributor.author | Green, Hillary F. | - |
dc.contributor.author | Liu, Tong | - |
dc.contributor.author | Chae, Pil Seok | - |
dc.contributor.author | Dror, Ron O. | - |
dc.contributor.author | Shaw, David E. | - |
dc.contributor.author | Weis, William I. | - |
dc.contributor.author | Wess, Juergen | - |
dc.contributor.author | Kobilka, Brian K. | - |
dc.date.accessioned | 2021-06-23T07:53:54Z | - |
dc.date.available | 2021-06-23T07:53:54Z | - |
dc.date.created | 2021-01-21 | - |
dc.date.issued | 2012-02 | - |
dc.identifier.issn | 0028-0836 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/33197 | - |
dc.description.abstract | Acetylcholine, the first neurotransmitter to be identified(1), exerts many of its physiological actions via activation of a family of G-protein-coupled receptors (GPCRs) known as muscarinic acetylcholine receptors (mAChRs). Although the five mAChR subtypes (M1-M5) share a high degree of sequence homology, they show pronounced differences in G-protein coupling preference and the physiological responses they mediate(2-4). Unfortunately, despite decades of effort, no therapeutic agents endowed with clear mAChR subtype selectivity have been developed to exploit these differences(5,6). We describe here the structure of the G(q/11)-coupled M3 mAChR ('M3 receptor', from rat) bound to the bronchodilator drug tiotropium and identify the binding mode for this clinically important drug. This structure, together with that of the G(i/o)-coupled M2 receptor(7), offers possibilities for the design of mAChR subtype-selective ligands. Importantly, the M3 receptor structure allows a structural comparison between two members of a mammalian GPCR subfamily displaying different G-protein coupling selectivities. Furthermore, molecular dynamics simulations suggest that tiotropium binds transiently to an allosteric site en route to the binding pocket of both receptors. These simulations offer a structural view of an allosteric binding mode for an orthosteric GPCR ligand and provide additional opportunities for the design of ligands with different affinities or binding kinetics for different mAChR subtypes. Our findings not only offer insights into the structure and function of one of the most important GPCR families, but may also facilitate the design of improved therapeutics targeting these critical receptors. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | Nature Publishing Group | - |
dc.title | Structure and dynamics of the M3 muscarinic acetylcholine receptor | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Chae, Pil Seok | - |
dc.identifier.doi | 10.1038/nature10867 | - |
dc.identifier.scopusid | 2-s2.0-84863115467 | - |
dc.identifier.wosid | 000300770500056 | - |
dc.identifier.bibliographicCitation | Nature, v.482, no.7386, pp.552 - 556 | - |
dc.relation.isPartOf | Nature | - |
dc.citation.title | Nature | - |
dc.citation.volume | 482 | - |
dc.citation.number | 7386 | - |
dc.citation.startPage | 552 | - |
dc.citation.endPage | 556 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | CONFORMATIONAL-CHANGES | - |
dc.subject.keywordPlus | MOLECULAR-DYNAMICS | - |
dc.subject.keywordPlus | FORCE-FIELD | - |
dc.subject.keywordPlus | AMINO-ACID | - |
dc.subject.keywordPlus | BINDING | - |
dc.subject.keywordPlus | IDENTIFICATION | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | SITE | - |
dc.subject.keywordPlus | SELECTIVITY | - |
dc.subject.keywordPlus | VALIDATION | - |
dc.identifier.url | https://www.nature.com/articles/nature10867 | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
55 Hanyangdeahak-ro, Sangnok-gu, Ansan, Gyeonggi-do, 15588, Korea+82-31-400-4269 sweetbrain@hanyang.ac.kr
COPYRIGHT © 2021 HANYANG UNIVERSITY. ALL RIGHTS RESERVED.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.