Structural insights into the regulation of monomeric and dimeric apelin receptor

doi:10.1038/s41467-024-55555-6

KMS > iHuman研究所

	Structural insights into the regulation of monomeric and dimeric apelin receptor
	Yue, Yang1 ; Liu, Lier1,2 ; Wu, Lijie1 ; Xu, Chanjuan 3,4; Na, Man1,2 ; Liu, Shenhui1,2 ; Liu, Yuxuan 3,4; Li, Fei1 ; Liu, Junlin1 ; Shi, Songting 5; Lei, Hui 5; Zhao, Minxuan1,2 ; Yang, Tianjie 6; Ji, Wei 6; Wang, Arthur 7; Hanson, Michael A.8; Stevens, Raymond C.5; Liu, Jianfeng 3,4; Xu, Fei1,2,7,9
	2025-01-02
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
EISSN	2041-1723
卷号	16 期号:1
DOI	10.1038/s41467-024-55555-6
摘要	The apelin receptor (APJR) emerges as a promising drug target for cardiovascular health and muscle regeneration. While prior research unveiled the structural versatility of APJR in coupling to Gi proteins as a monomer or dimer, the dynamic regulation within the APJR dimer during activation remains poorly understood. In this study, we present the structures of the APJR dimer and monomer complexed with its endogenous ligand apelin-13. In the dimeric structure, apelin-13 binds exclusively to one protomer that is coupled with Gi proteins, revealing a distinct ligand-binding behavior within APJR homodimers. Furthermore, binding of an antagonistic antibody induces a more compact dimerization by engaging both protomers. Notably, structural analyses of the APJR dimer complexed with an agonistic antibody, with or without Gi proteins, suggest that G protein coupling may promote the dissociation of the APJR dimer during activation. These findings underscore the intricate interplay between ligands, dimerization, and G protein coupling in regulating APJR signaling pathways.
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收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China (National Science Foundation of China)["32071194","32330049"]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:001390087300047
出版者	NATURE PORTFOLIO
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/470980
专题	iHuman研究所生命科学与技术学院 iHuman研究所_公共科研平台_IT平台 iHuman研究所_公共科研平台_昆虫细胞培养平台 iHuman研究所_PI研究组_徐菲组 iHuman研究所_科学装置(X)_膜蛋白同步辐射线站生命科学与技术学院_硕士生生命科学与技术学院_博士生生命科学与技术学院_本科生
通讯作者	Liu, Jianfeng; Xu, Fei
作者单位	1.ShanghaiTech Univ, iHuman Inst, Shanghai, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 3.Huazhong Univ Sci & Technol HUST, Coll Life Sci & Technol, Key Lab Mol Biophys MOE, Wuhan, Peoples R China 4.Huazhong Univ Sci & Technol HUST, Coll Life Sci & Technol, Int Res Ctr Sensory Biol & Technol MOST, Wuhan, Peoples R China 5.Struct Therapeut, South San Francisco, CA USA 6.Chinese Acad Sci, Inst Biophys, Beijing, Peoples R China 7.JiKang Therapeut, Shanghai, Peoples R China 8.Univ Miami, Phillip & Patricia Frost Inst Chem & Mol Sci, Coral Gables, FL USA 9.Shanghai Clin Res & Trial Ctr, Shanghai, Peoples R China
第一作者单位	iHuman研究所
通讯作者单位	iHuman研究所; 生命科学与技术学院
第一作者的第一单位	iHuman研究所
推荐引用方式 GB/T 7714	Yue, Yang,Liu, Lier,Wu, Lijie,et al. Structural insights into the regulation of monomeric and dimeric apelin receptor[J]. NATURE COMMUNICATIONS,2025,16(1).
APA	Yue, Yang.,Liu, Lier.,Wu, Lijie.,Xu, Chanjuan.,Na, Man.,...&Xu, Fei.(2025).Structural insights into the regulation of monomeric and dimeric apelin receptor.NATURE COMMUNICATIONS,16(1).
MLA	Yue, Yang,et al."Structural insights into the regulation of monomeric and dimeric apelin receptor".NATURE COMMUNICATIONS 16.1(2025).