Hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptor

doi:10.1016/j.csbj.2022.11.039

	Hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptor
	He, Xinheng 1,2,3; Duan, Jia 1,2,3; Ji, Yujie 1,2,3; Zhao, Lifen 1,2; Jiang, Hualiang1,2,3,4,5,6 ; Jiang, Yi1,2,5,6 ; Xu, H. Eric 1,2,3; Cheng, Xi 1,2,3,4
	2022-01
发表期刊	COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL (IF:4.4[JCR-2023],5.0[5-Year])
ISSN	2001-0370
EISSN	2001-0370
卷号	20 页码:6503-6511
发表状态	已发表
DOI	10.1016/j.csbj.2022.11.039
摘要	Luteinizing hormone-choriogonadotropin receptor (LHCGR), a class A G protein-coupled receptor (GPCR), plays a pivotal role in the maturation of reproductive organs and embryonic development. Compared with other GPCRs, the subfamily of LHCGR has a large extracellular domain (ECD) to interact with glycoprotein hormones. A unique hinge region connects the ECD and transmembrane domain (TMD) to transfer the activation signal. However, the signal transmission mechanism remains largely unknown. Here, both molecular dynamics simulation and evolutional analysis were applied to explore the effect of the hinge region on signal transmission. The glycoprotein hormone determined specific hinge region conformations, including the position of a long hinge loop and the ECD-TMD interface. With the hormone, the hinge region showed a characteristic rotation and displayed an active-like conformational landscape of the ECD-TMD interface with an extended TMD. The active-like hinge region conformation transduces the hormone binding signal downwards from ECD to TMD. The relationship between the hinge region and the intracelluar G protein-binding pocket was also inferred. The hinge region-mediated signal transmission mechanism offers a deeper understanding of LHCGR and provides insights into the elucidation of GPCR activation. © 2022 The Author(s)
关键词	Activation analysis Biochemistry Chemical activation Glycoproteins Hormones Proteins Dynamics simulation Evolutionary analyse Extracellular domains G protein coupled receptors Glycoprotein hormone receptors Molecular dynamic simulation Protein dynamics Signal transmission Trans-membrane domains Transmembrane domain
URL	查看原文
收录类别	EI ; SCI
语种	英语
资助项目	Lin-gang Laboratory grant[LG202102-01-01] ; Ministry of Science and Technology (China)[2018YFA0507002] ; CAS Strategic Priority Research Program[XDB37030103] ; National Natural Science Foundation of China["32130022","32171187","82121005"]
WOS研究方向	Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology
WOS类目	Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology
WOS记录号	WOS:000913258100010
出版者	Elsevier B.V.
EI入藏号	20224913207911
EI主题词	Molecular dynamics
EI分类号	461.2 Biological Materials and Tissue Engineering ; 461.9 Biology ; 801.2 Biochemistry ; 801.4 Physical Chemistry ; 802.2 Chemical Reactions ; 804 Chemical Products Generally ; 804.1 Organic Compounds
原始文献类型	Journal article (JA)
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/256359
专题	免疫化学研究所_特聘教授组_蒋华良组生命科学与技术学院
通讯作者	Jiang, Yi; Xu, H. Eric; Cheng, Xi
作者单位	1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China 4.Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 6.Lingang Lab, Shanghai, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	He, Xinheng,Duan, Jia,Ji, Yujie,et al. Hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptor[J]. COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL,2022,20:6503-6511.
APA	He, Xinheng.,Duan, Jia.,Ji, Yujie.,Zhao, Lifen.,Jiang, Hualiang.,...&Cheng, Xi.(2022).Hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptor.COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL,20,6503-6511.
MLA	He, Xinheng,et al."Hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptor".COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL 20(2022):6503-6511.