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  2. 上海药物研究所
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Structural basis of FPR2 in recognition of A beta(42) and neuroprotection by humanin

文献类型：期刊论文

作者Zhu, Ya2; Lin, Xiaowen2,3,4; Zong, Xin2,4; Han, Shuo2,3,4; Wang, Mu2,5; Su, Yuxuan1; Ma, Limin2; Chu, Xiaojing2; Yi, Cuiying2; Zhao, Qiang2,4,6
刊名NATURE COMMUNICATIONS
出版日期2022-04-01
卷号13期号:1页码:10
DOI10.1038/s41467-022-29361-x
通讯作者Zhao, Qiang(zhaoq@simm.ac.cn) ; Wu, Beili(beiliwu@simm.ac.cn)
英文摘要Formyl peptide receptor 2 (FPR2) has been shown to mediate the cytotoxic effects of the beta amyloid peptide A beta(42) and serves as a receptor for humanin, a peptide that protects neuronal cells from damage by A beta(42), implying its involvement in the pathogenesis of Alzheimer's disease (AD). However, the interaction pattern between FPR2 and A beta(42) or humanin remains unknown. Here we report the structures of FPR2 bound to G(i) and A beta(42) or N-formyl humanin (fHN). Combined with functional data, the structures reveal two critical regions that govern recognition and activity of A beta(42) and fHN, including a polar binding cavity within the receptor helical bundle and a hydrophobic binding groove in the extracellular region. In addition, the structures of FPR2 and FPR1 in complex with different formyl peptides were determined, providing insights into ligand recognition and selectivity of the FPR family. These findings uncover key factors that define the functionality of FPR2 in AD and other inflammatory diseases and would enable drug development. The formyl peptide receptor 2 (FPR2) is involved in the pathogenesis of Alzheimer's disease. Structures of FPR2 bound to A beta(42), humanin, or formyl peptides offer insight into A beta(42) neurotoxicity, humanin neuroprotection, and FPR ligand selectivity
WOS关键词PEPTIDE ; RECEPTOR-LIKE-1 ; RESPONSES ; DOMAIN
资助项目National Science Foundation of China[31730027] ; National Science Foundation of China[31825010] ; National Science Foundation of China[82121005] ; National Key R&D Program of China[2018YFA0507000] ; CAS Strategic Priority Research Program[XDB37030100] ; Shanghai Pilot Program for Basic Research-Chinese Academy of Sciences, Shanghai Branch[JCYJ-SHFY-2021-008]
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATURE PORTFOLIO
WOS记录号WOS:000777408600020
源URL[http://119.78.100.183/handle/2S10ELR8/299848]  
专题新药研究国家重点实验室
通讯作者Zhao, Qiang; Wu, Beili
作者单位1.China Pharmaceut Univ, Sch Basic Med & Clin Pharm, Nanjing, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, State Key Lab Drug Res, Shanghai, Peoples R China
3.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou, Peoples R China
4.Univ Chinese Acad Sci, Beijing, Peoples R China
5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, Zhongshan Inst Drug Discovery, Zhongshan, Peoples R China
推荐引用方式
GB/T 7714		 Zhu, Ya,Lin, Xiaowen,Zong, Xin,et al. Structural basis of FPR2 in recognition of A beta(42) and neuroprotection by humanin[J]. NATURE COMMUNICATIONS,2022,13(1):10.
APA Zhu, Ya.,Lin, Xiaowen.,Zong, Xin.,Han, Shuo.,Wang, Mu.,...&Wu, Beili.(2022).Structural basis of FPR2 in recognition of A beta(42) and neuroprotection by humanin.NATURE COMMUNICATIONS,13(1),10.
MLA Zhu, Ya,et al."Structural basis of FPR2 in recognition of A beta(42) and neuroprotection by humanin".NATURE COMMUNICATIONS 13.1(2022):10.

入库方式： OAI收割

来源：上海药物研究所

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