Molecular basis for the activation of PAF receptor by PAF
文献类型：期刊论文
| 作者 | Fan, Wenjia4,5; Xu, Youwei4; He, Xinheng3,4; Luo, Ping4; Zhu, Jingpeng4; Li, Junrui4; Wang, Ruolan3,4; Yuan, Qingning4; Wu, Kai2,4; Hu, Wen2,4 |
| 刊名 | CELL REPORTS
 |
| 出版日期 | 2024-07-23 |
| 卷号 | 43期号:7页码:17 |
| ISSN号 | 2211-1247 |
| DOI | 10.1016/j.celrep.2024.114422 |
| 通讯作者 | Wang, Yue(wangyue1@simm.ac.cn) ; Xu, H. Eric(eric.xu@simm.ac.cn) ; Zhuang, Youwen(youwen_zhuang@sjtu.edu.cn) |
| 英文摘要 | Platelet -activating factor (PAF) is a potent phospholipid mediator crucial in multiple inflammatory and immune responses through binding and activating the PAF receptor (PAFR). However, drug development targeting the PAFR has been limited, partly due to an incomplete understanding of its activation mechanism. Here, we present a 2.9-A & ring; structure of the PAF-bound PAFR-Gi complex. Structural and mutagenesis analyses unveil a specific binding mode of PAF, with the choline head forming cation -p interactions within PAFR hydrophobic pocket, while the alkyl tail penetrates deeply into an aromatic cleft between TM4 and TM5. Binding of PAF modulates conformational changes in key motifs of PAFR, triggering the outward movement of TM6, TM7, and helix 8 for G protein coupling. Molecular dynamics simulation suggests a membrane -side pathway for PAF entry into PAFR via the TM4-TM5 cavity. By providing molecular insights into PAFR signaling, this work contributes a foundation for developing therapeutic interventions targeting PAF signal axis. |
| WOS关键词 | SYSTEM ; TOOLS |
| 资助项目 | National Key R&D Program of China[2022YFC2703105] ; National Key R&D Program of China[2022YFA1302900] ; National Key R&D Program of China[2019YFA0904200] ; Young Elite Scientists Sponsorship Program by CAST[2023QNRC001] ; National Natural Science Foundation of China[32301006] ; National Natural Science Foundation of China[32130022] ; National Natural Science Foundation of China[82121005] ; CAS Strategic Priority Research Program[XDB37030103] ; Shanghai Municipal Science and Technology Major Project ; State Key Laboratory of Drug Research[SKLDR-2023-TT-04] ; Natural Science Foundation of Shanghai, China[23ZR1475300] ; Sailing Program of Shanghai Venus Project[23YF1456700] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences[2023298] ; Special Research Assistant Project of Chinese Academy of Sciences ; Special Research Assistant Project of Chinese Academy of Sciences ; [LG-GG-202204-01] |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:001262653400001 |
| 出版者 | CELL PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/312288]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Wang, Yue; Xu, H. Eric; Zhuang, Youwen |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Med Bioinformat Ctr, Sch Med, Shanghai 200025, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Adv Electron Microscope Ctr, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210046, Peoples R China |
| 推荐引用方式 GB/T 7714 | Fan, Wenjia,Xu, Youwei,He, Xinheng,et al. Molecular basis for the activation of PAF receptor by PAF[J]. CELL REPORTS,2024,43(7):17. |
| APA | Fan, Wenjia.,Xu, Youwei.,He, Xinheng.,Luo, Ping.,Zhu, Jingpeng.,...&Zhuang, Youwen.(2024).Molecular basis for the activation of PAF receptor by PAF.CELL REPORTS,43(7),17. |
| MLA | Fan, Wenjia,et al."Molecular basis for the activation of PAF receptor by PAF".CELL REPORTS 43.7(2024):17. |
入库方式： OAI收割
来源：上海药物研究所
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