Molecular mechanism underlying non-discriminatory recognition of relaxin-3 by RXFP3 and RXFP4
文献类型：期刊论文
| 作者 | Chen, Yan7; Zhou, Qingtong6,7; Yan, Shiyu4,5; Yan, Jiahui3,5; Yang, Dehua3,4,5 ; Chen, Jian3; Wang, Ming-Wei1,2,6,7
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| 刊名 | COMMUNICATIONS BIOLOGY
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| 出版日期 | 2025-05-23 |
| 卷号 | 8期号:1页码:13 |
| DOI | 10.1038/s42003-025-08220-7 |
| 通讯作者 | Wang, Ming-Wei(mwwang@simm.ac.cn) |
| 英文摘要 | The human relaxin family peptide receptors RXFP3 and RXFP4 play important physiological roles through interactions with endogenous hormones, relaxin-3 and insulin-like peptide 5 (INSL5). They are implicated in certain neurological and metabolic disorders. While INSL5 only activates RXFP4, relaxin-3 is recognized by both receptors. Here, we report the cryo-electron microscopy structures of RXFP3-Gi complexes bound by relaxin-3 or a small-molecule dual agonist (compound 4), and relaxin-3 in complex with RXFP4-Gi, with global resolutions of 2.91 & Aring;, 2.95 & Aring;, and 3.10 & Aring;, respectively. It is found that relaxin-3 adopts a conserved binding conformation within the transmembrane domain (TMD) bundle of RXFP3 and RXFP4, where the C-terminal tip residues of its B chain, R26 and W27, make extensive contacts with conserved receptor residues, thereby activating RXFP3 and RXFP4. Compound 4 mimics these key interactions by binding to both receptors. In contrast, the C-terminal residues composition and TMD-binding angle of INSL5 in RXFP4 differ significantly from that of relaxin-3, ensuring its selectivity for RXFP4. These findings deepen our understanding about the structural basis of ligand recognition and selectivity in this G protein-coupled receptor subfamily. |
| WOS关键词 | RECEPTOR ; LIGAND ; ALCOHOL ; SYSTEM ; CONSUMPTION ; PEPTIDE ; AROUSAL ; NEURONS ; STRESS |
| 资助项目 | National Natural Science Foundation of China (National Science Foundation of China)[82073904] ; National Natural Science Foundation of China (National Science Foundation of China)[82121005] ; National Natural Science Foundation of China (National Science Foundation of China)[21704064] ; National Natural Science Foundation of China (National Science Foundation of China)[2021ZD0203400] ; National Natural Science Foundation of China[ZDKJ2021028] ; Hainan Provincial Major Science and Technology Project ; Chinese Academy of Sciences |
| WOS研究方向 | Life Sciences & Biomedicine - Other Topics ; Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001494432900007 |
| 出版者 | NATURE PORTFOLIO |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/317950]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wang, Ming-Wei |
| 作者单位 | 1.Hainan Med Univ, Sch Pharm, Engn Res Ctr Trop Med Innovat & Transformat, Minist Educ, Haikou, Peoples R China 2.Res Ctr Deepsea Bioresources, Sanya, Peoples R China 3.Fudan Univ, Sch Pharm, Shanghai, Peoples R China 4.Univ Chinese Acad Sci, Beijing, Peoples R China 5.Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, Shanghai, Peoples R China 6.Fudan Univ, Sch Basic Med Sci, Dept Pharmacol, Shanghai, Peoples R China 7.Shanghai Jiao Tong Univ, Res Ctr Med Struct Biol, Natl Res Ctr Translat Med Shanghai, State Key Lab Med Genom,Ruijin Hosp,Sch Med, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Yan,Zhou, Qingtong,Yan, Shiyu,et al. Molecular mechanism underlying non-discriminatory recognition of relaxin-3 by RXFP3 and RXFP4[J]. COMMUNICATIONS BIOLOGY,2025,8(1):13. |
| APA | Chen, Yan.,Zhou, Qingtong.,Yan, Shiyu.,Yan, Jiahui.,Yang, Dehua.,...&Wang, Ming-Wei.(2025).Molecular mechanism underlying non-discriminatory recognition of relaxin-3 by RXFP3 and RXFP4.COMMUNICATIONS BIOLOGY,8(1),13. |
| MLA | Chen, Yan,et al."Molecular mechanism underlying non-discriminatory recognition of relaxin-3 by RXFP3 and RXFP4".COMMUNICATIONS BIOLOGY 8.1(2025):13. |
入库方式： OAI收割
来源：上海药物研究所
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