Structural basis for signal recognition and transduction by platelet-activating-factor receptor

doi:10.1038/s41594-018-0068-y

KMS > iHuman研究所

	Structural basis for signal recognition and transduction by platelet-activating-factor receptor
	Cao, Can 1,4; Tan, Qiuxiang 2,3,4; Xu, Chanjuan 5,6; He, Lingli 1; Yang, Linlin 7; Zhou, Ye 1,4; Zhou, Yiwei 5,6; Qiao, Anna 3,4; Lu, Minmin 3,4; Yi, Cuiying 2; Han, Gye Won 8; Wang, Xianping 1; Li, Xuemei 1; Yang, Huaiyu 9; Rao, Zihe 1; Jiang, Hualiang 2,3,9; Zhao, Yongfang 1; Liu, Jianfeng 5,6; Stevens, Raymond C.10,11 ; Zhao, Qiang 2,3,4,12; Zhang, Xuejun C.1,4; Wu, Beili2,4,11,12
	2018-06
发表期刊	NATURE STRUCTURAL & MOLECULAR BIOLOGY (IF:12.5[JCR-2023],13.1[5-Year])
ISSN	1545-9993
卷号	25 期号:6 页码:488-+
发表状态	已发表
DOI	10.1038/s41594-018-0068-y
摘要	Platelet-activating-factor receptor (PAFR) responds to platelet-activating factor (PAF), a phospholipid mediator of cell-to-cell communication that exhibits diverse physiological effects. PAFR is considered an important drug target for treating asthma, inflammation and cardiovascular diseases. Here we report crystal structures of human PAFR in complex with the antagonist SR 27417 and the inverse agonist ABT-491 at 2.8-A and 2.9-A resolution, respectively. The structures, supported by molecular docking of PAF, provide insights into the signal-recognition mechanisms of PAFR. The PAFR-SR 27417 structure reveals an unusual conformation showing that the intracellular tips of helices II and IV shift outward by 13A and 44, respectively, and helix VIII adopts an inward conformation. The PAFR structures, combined with single-molecule FRET and cell-based functional assays, suggest that the conformational change in the helical bundle is ligand dependent and plays a critical role in PAFR activation, thus greatly extending knowledge about signaling by G-protein-coupled receptors.
收录类别	SCI ; SCIE
语种	英语
资助项目	Program of Introducing Talents of Discipline to the Universities of the Ministry of Education[B08029]
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS记录号	WOS:000434470800009
出版者	NATURE PUBLISHING GROUP
WOS关键词	PROTEIN-COUPLED-RECEPTOR ; CRYO-EM STRUCTURE ; HUMAN P2Y(12) RECEPTOR ; CRYSTAL-STRUCTURE ; FORCE-FIELD ; CONFORMATIONAL-CHANGES ; GLP-1 RECEPTOR ; HIGHLY POTENT ; COMPLEX ; ANTAGONIST
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/27439
专题	iHuman研究所 iHuman研究所_特聘教授组_Raymond Stevens组生命科学与技术学院_特聘教授组_吴蓓丽组
通讯作者	Zhang, Xuejun C.; Wu, Beili
作者单位	1.Chinese Acad Sci, Natl Ctr Prot Sci Beijing, Inst Biophys, Natl Lab Biomacromol,CAS Ctr Excellence Biomacrom, Beijing, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China 4.Univ Chinese Acad Sci, Beijing, Peoples R China 5.Huazhong Univ Sci & Technol, Minist Educ, Coll Life Sci & Technol, Collaborat Innovat Ctr Genet & Dev, Wuhan, Hubei, Peoples R China 6.Huazhong Univ Sci & Technol, Minist Educ, Key Lab Mol Biophys, Wuhan, Hubei, Peoples R China 7.Zhengzhou Univ, Sch Basic Med Sci, Dept Pharmacol, Zhengzhou, Henan, Peoples R China 8.Univ Southern Calif, Dept Chem, Bridge Inst, Los Angeles, CA USA 9.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai, Peoples R China 10.ShanghaiTech Univ, iHuman Inst, Shanghai, Peoples R China 11.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 12.Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Beijing, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Cao, Can,Tan, Qiuxiang,Xu, Chanjuan,et al. Structural basis for signal recognition and transduction by platelet-activating-factor receptor[J]. NATURE STRUCTURAL & MOLECULAR BIOLOGY,2018,25(6):488-+.
APA	Cao, Can.,Tan, Qiuxiang.,Xu, Chanjuan.,He, Lingli.,Yang, Linlin.,...&Wu, Beili.(2018).Structural basis for signal recognition and transduction by platelet-activating-factor receptor.NATURE STRUCTURAL & MOLECULAR BIOLOGY,25(6),488-+.
MLA	Cao, Can,et al."Structural basis for signal recognition and transduction by platelet-activating-factor receptor".NATURE STRUCTURAL & MOLECULAR BIOLOGY 25.6(2018):488-+.