Mechanism of hormone and allosteric agonist mediated activation of follicle stimulating hormone receptor

doi:10.1038/s41467-023-36170-3

	Mechanism of hormone and allosteric agonist mediated activation of follicle stimulating hormone receptor
	Duan, Jia 1,2; Xu, Peiyu 1; Zhang, Huibing 3,4,5,6; Luan, Xiaodong 7,8,9,10; Yang, Jiaqi 1; He, Xinheng 1,2; Mao, Chunyou 3,4,5,6; Shen, Dan-Dan 3,4,5,6; Ji, Yujie 1,2; Cheng, Xi 1; Jiang, Hualiang1,2,11,12 ; Jiang, Yi11,12 ; Zhang, Shuyang 7,8,9,10; Zhang, Yan 3,4,5,6; Xu, H. Eric1,2,12
	2023-12-01
发表期刊	NATURE COMMUNICATIONS;
ISSN	2041-1723
卷号	14 期号:1
DOI	10.1038/s41467-023-36170-3
摘要	Follicle stimulating hormone (FSH) is an essential glycoprotein hormone for human reproduction, which functions are mediated by a G protein-coupled receptor, FSHR. Aberrant FSH-FSHR signaling causes infertility and ovarian hyperstimulation syndrome. Here we report cryo-EM structures of FSHR in both inactive and active states, with the active structure bound to FSH and an allosteric agonist compound 21 f. The structures of FSHR are similar to other glycoprotein hormone receptors, highlighting a conserved activation mechanism of hormone-induced receptor activation. Compound 21 f formed extensive interactions with the TMD to directly activate FSHR. Importantly, the unique residue H6157.42 in FSHR plays an essential role in determining FSHR selectivity for various allosteric agonists. Together, our structures provide a molecular basis of FSH and small allosteric agonist-mediated FSHR activation, which could inspire the design of FSHR-targeted drugs for the treatment of infertility and controlled ovarian stimulation for in vitro fertilization.
学科门类	Chemistry (all) ; Biochemistry, Genetics and Molecular Biology (all) ; Multidisciplinary ; Physics and Astronomy (all)
URL	查看原文
收录类别	SCOPUS
语种	英语
原始文献类型	Article
Scopus 记录号	2-s2.0-85147127653
来源库	SCOPUS
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/286457
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生命科学与技术学院_特聘教授组_徐华强组
作者单位	1.State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China; 2.University of Chinese Academy of Sciences,Beijing,100049,China; 3.Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Zhejiang,Hangzhou,China; 4.Liangzhu Laboratory,Zhejiang University Medical Center,Zhejiang,Hangzhou,China; 5.MOE Frontier Science Center for Brain Research and Brain-Machine Integration,Zhejiang University School of Medicine,Zhejiang,Hangzhou,China; 6.Zhejiang Provincial Key Laboratory of Immunity and Inflammatory diseases,Zhejiang,Hangzhou,China; 7.Department of Cardiology,Peking Union Medical College Hospital,Peking Union Medical College and Chinese Academy of Medical Sciences,Beijing,China; 8.Medical Research Center,Peking Union Medical College Hospital,Peking Union Medical College and Chinese Academy of Medical Sciences,Beijing,China; 9.School of medicine,Tsinghua university,Beijing,China; 10.Tsinghua-Peking Center for life science,Tsinghua university,Beijing,China; 11.Lingang Laboratory,Shanghai,200031,China; 12.School of Life Science and Technology,ShanghaiTech University,Shanghai,201210,China
推荐引用方式 GB/T 7714	Duan, Jia,Xu, Peiyu,Zhang, Huibing,et al. Mechanism of hormone and allosteric agonist mediated activation of follicle stimulating hormone receptor[J]. NATURE COMMUNICATIONS;,2023,14(1).
APA	Duan, Jia.,Xu, Peiyu.,Zhang, Huibing.,Luan, Xiaodong.,Yang, Jiaqi.,...&Xu, H. Eric.(2023).Mechanism of hormone and allosteric agonist mediated activation of follicle stimulating hormone receptor.NATURE COMMUNICATIONS;,14(1).
MLA	Duan, Jia,et al."Mechanism of hormone and allosteric agonist mediated activation of follicle stimulating hormone receptor".NATURE COMMUNICATIONS; 14.1(2023).