Structural basis for signal recognition and transduction by platelet-activating-factor receptor
文献类型：期刊论文
| 作者 | Cao, Can11,12; Tan, Qiuxiang1,10,11; Xu, Chanjuan2,3; He, Lingli12; Yang, Linlin4; Zhou, Ye11,12; Zhou, Yiwei2,3; Qiao, Anna1,11; Lu, Minmin1,11; Yi, Cuiying10 |
| 刊名 | NATURE STRUCTURAL & MOLECULAR BIOLOGY
 |
| 出版日期 | 2018-06 |
| 卷号 | 25期号:6页码:488-+ |
| ISSN号 | 1545-9993 |
| DOI | 10.1038/s41594-018-0068-y |
| 文献子类 | Article |
| 英文摘要 | 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. |
| 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 |
| 资助项目 | National Key RAMP[00000000] ; D Program of China[2018YFA0507000] ; CAS Strategic Priority Research Program[XDB08020000] ; Key Research Program of Frontier Sciences, CAS[QYZDB-SSW-SMC024] ; Key Research Program of Frontier Sciences, CAS[QYZDB-SSW-SMC054] ; National Science Foundation of China[81525024] ; National Science Foundation of China[31301163] ; 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 |
| 语种 | 英语 |
| 出版者 | NATURE PUBLISHING GROUP |
| WOS记录号 | WOS:000434470800009 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279724]  |
| 专题 | 药物靶标结构与功能中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Zhang, Xuejun C.; Wu, Beili |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China; 2.Huazhong Univ Sci & Technol, Minist Educ, Coll Life Sci & Technol, Collaborat Innovat Ctr Genet & Dev, Wuhan, Hubei, Peoples R China; 3.Huazhong Univ Sci & Technol, Minist Educ, Key Lab Mol Biophys, Wuhan, Hubei, Peoples R China; 4.Zhengzhou Univ, Sch Basic Med Sci, Dept Pharmacol, Zhengzhou, Henan, Peoples R China; 5.Univ Southern Calif, Dept Chem, Bridge Inst, Los Angeles, CA USA; 6.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai, Peoples R China; 7.ShanghaiTech Univ, iHuman Inst, Shanghai, Peoples R China; 8.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 9.Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Beijing, Peoples R China 10.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China; |
| 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-+. |
入库方式： OAI收割
来源：上海药物研究所
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