Structure of the Angiotensin Receptor Revealed by Serial Femtosecond Crystallography

doi:10.1016/j.cell.2015.04.011

KMS > iHuman研究所 > 特聘教授组 > Raymond Stevens组

	Structure of the Angiotensin Receptor Revealed by Serial Femtosecond Crystallography
	Zhang, Haitao 1; Unal, Hamiyet 2; Gati, Cornelius 3; Han, Gye Won 4; Liu, Wei 5; Zatsepin, Nadia A.6; James, Daniel 6; Wang, Dingjie 6; Nelson, Garrett 6; Weierstall, Uwe 6; Sawaya, Michael R.7; Xu, Qingping 8; Messerschmidt, Marc 9; Williams, Garth J.10; Boutet, Sebastien 10; Yefanov, Oleksandr M.3; White, Thomas A.3; Wang, Chong 11; Ishchenko, Andrii 4; Tirupula, Kalyan C.2; Desnoyer, Russell 2; Coe, Jesse 5; Conrad, Chelsie E.5; Fromme, Petra 5; Stevens, Raymond C.1,4,12 ; Katritch, Vsevolod 1; Karnik, Sadashiva S.2; Cherezov, Vadim 4
	2015-05-07
发表期刊	CELL (IF:45.5[JCR-2023],49.0[5-Year])
ISSN	0092-8674
卷号	161 期号:4 页码:833-844
发表状态	已发表
DOI	10.1016/j.cell.2015.04.011
摘要	Angiotensin II type 1 receptor (AT(1)R) is a G protein-coupled receptor that serves as a primary regulator for blood pressure maintenance. Although several anti-hypertensive drugs have been developed as AT(1)R blockers (ARBs), the structural basis for AT(1)R ligand-binding and regulation has remained elusive, mostly due to the difficulties of growing high-quality crystals for structure determination using synchrotron radiation. By applying the recently developed method of serial femtosecond crystallography at an X-ray free-electron laser, we successfully determined the room-temperature crystal structure of the human AT(1)R in complex with its selective antagonist ZD7155 at 2.9-angstrom resolution. The AT(1)R-ZD7155 complex structure revealed key structural features of AT(1)R and critical interactions for ZD7155 binding. Docking simulations of the clinically used ARBs into the AT(1)R structure further elucidated both the common and distinct binding modes for these antihypertensive drugs. Our results thereby provide fundamental insights into AT(1)R structure-function relationship and structure-based drug design.
收录类别	SCI
语种	英语
资助项目	BMBF[FKZ 05K12CH1]
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:000354175200016
出版者	CELL PRESS
WOS关键词	II TYPE-1 RECEPTOR ; AT(1A) CARBOXYL-TERMINUS ; LIPIDIC CUBIC PHASE ; AGONISTIC AUTOANTIBODIES ; PROXIMAL REGION ; OPIOID RECEPTOR ; BINDING ; GPCR ; ACTIVATION ; MANAGEMENT
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/2212
专题	iHuman研究所_特聘教授组_Raymond Stevens组 iHuman研究所
通讯作者	Cherezov, Vadim
作者单位	1.Univ So Calif, Dept Biol Sci, Bridge Inst, Los Angeles, CA 90089 USA 2.Cleveland Clin, Lerner Res Inst, Dept Mol Cardiol, Cleveland, OH 44195 USA 3.DESY, Ctr Free Elect Laser Sci, D-22607 Hamburg, Germany 4.Univ So Calif, Bridge Inst, Dept Chem, Los Angeles, CA 90089 USA 5.Arizona State Univ, Ctr Appl Struct Discovery, Biodesign Inst, Dept Chem & Biochem, Tempe, AZ 85287 USA 6.Arizona State Univ, Dept Phys, Tempe, AZ 85287 USA 7.Univ Calif Los Angeles, UCLA DOE Inst Genom & Prote, Dept Chem & Biochem, Los Angeles, CA 90095 USA 8.SLAC Natl Accelerator Lab, Stanford Synchrotron Radiat Light Source, Joint Ctr Struct Genom, Menlo Pk, CA 94025 USA 9.BioXFEL Sci & Technol Ctr, Buffalo, NY 14203 USA 10.SLAC Natl Accelerator Lab, Linac Coherent Light Source, Menlo Pk, CA 94025 USA 11.Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA 12.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Haitao,Unal, Hamiyet,Gati, Cornelius,et al. Structure of the Angiotensin Receptor Revealed by Serial Femtosecond Crystallography[J]. CELL,2015,161(4):833-844.
APA	Zhang, Haitao.,Unal, Hamiyet.,Gati, Cornelius.,Han, Gye Won.,Liu, Wei.,...&Cherezov, Vadim.(2015).Structure of the Angiotensin Receptor Revealed by Serial Femtosecond Crystallography.CELL,161(4),833-844.
MLA	Zhang, Haitao,et al."Structure of the Angiotensin Receptor Revealed by Serial Femtosecond Crystallography".CELL 161.4(2015):833-844.