气候变化领域集成服务门户(CCPortal): Angiotensin and biased analogs induce structurally distinct active conformations within a GPCR

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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 receptor beta arrestin G protein coupled receptor biochemistry crystal chemistry crystal structure physiological response protein signaling allosterism alpha helix amino terminal sequence Article binding affinity binding site carboxy terminal sequence conformational transition crystallization hydrogen bond molecular dynamics priority journal protein binding protein conformation protein protein interaction protein stability signal transduction thermostability
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).