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DOI | 10.1126/science.aay9813 |
Angiotensin and biased analogs induce structurally distinct active conformations within a GPCR | |
Wingler L.M.; Skiba M.A.; McMahon C.; Staus D.P.; Kleinhenz A.L.W.; Suomivuori C.-M.; Latorraca N.R.; Dror R.O.; Lefkowitz R.J.; Kruse A.C. | |
发表日期 | 2020 |
ISSN | 0036-8075 |
起始页码 | 888 |
结束页码 | 892 |
卷号 | 367期号:6480 |
英文摘要 | Biased agonists of G protein-coupled receptors (GPCRs) preferentially activate a subset of downstream signaling pathways. In this work, we present crystal structures of angiotensin II type 1 receptor (AT1R) (2.7 to 2.9 angstroms) bound to three ligands with divergent bias profiles: the balanced endogenous agonist angiotensin II (AngII) and two strongly b-arrestin-biased analogs. Compared with other ligands, AngII promotes more-substantial rearrangements not only at the bottom of the ligand-binding pocket but also in a key polar network in the receptor core, which forms a sodium-binding site in most GPCRs. Divergences from the family consensus in this region, which appears to act as a biased signaling switch, may predispose the AT1R and certain other GPCRs (such as chemokine receptors) to adopt conformations that are capable of activating b-arrestin but not heterotrimeric Gq protein signaling. © 2020 American Association for the Advancement of Science. All rights reserved. |
关键词 | angiotensin 1 receptorbeta arrestinG protein coupled receptorbiochemistrycrystal chemistrycrystal structurephysiological responseproteinsignalingallosterismalpha helixamino terminal sequenceArticlebinding affinitybinding sitecarboxy terminal sequenceconformational transitioncrystallizationhydrogen bondmolecular dynamicspriority journalprotein bindingprotein conformationprotein protein interactionprotein stabilitysignal transductionthermostability |
语种 | 英语 |
来源机构 | Science |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/133689 |
推荐引用方式 GB/T 7714 | Wingler L.M.,Skiba M.A.,McMahon C.,et al. Angiotensin and biased analogs induce structurally distinct active conformations within a GPCR[J]. Science,2020,367(6480). |
APA | Wingler L.M..,Skiba M.A..,McMahon C..,Staus D.P..,Kleinhenz A.L.W..,...&Kruse A.C..(2020).Angiotensin and biased analogs induce structurally distinct active conformations within a GPCR.,367(6480). |
MLA | Wingler L.M.,et al."Angiotensin and biased analogs induce structurally distinct active conformations within a GPCR".367.6480(2020). |
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