Structures of human mGlu2 and mGlu7 homo- and heterodimers

doi:10.1038/s41586-021-03641-w

	Structures of human mGlu2 and mGlu7 homo- and heterodimers
	Du, Juan 1,2,3; Wang, Dejian 1,4; Fan, Hongcheng 4,5; Xu, Chanjuan 6; Tai, Linhua 4,5; Lin, Shuling 2,4; Han, Shuo 1; Tan, Qiuxiang 2; Wang, Xinwei 2,4; Xu, Tuo 1,4; Zhang, Hui 2,4; Chu, Xiaojing 2; Yi, Cuiying 1; Liu, Peng 6; Wang, Xiaomei 6; Zhou, Yu 1,4; Pin, Jean-Philippe 7; Rondard, Philippe 7; Liu, Hong1,3,4,8 ; Liu, Jianfeng 6,9; Sun, Fei 4,5,9,10; Wu, Beili2,3,4,8 ; Zhao, Qiang 1,4,11
	2021
发表期刊	NATURE (IF:50.5[JCR-2023],54.4[5-Year])
ISSN	0028-0836
EISSN	1476-4687
卷号	594 期号:7864 页码:589-+
DOI	10.1038/s41586-021-03641-w
摘要	The metabotropic glutamate receptors (mGlus) are involved in the modulation of synaptic transmission and neuronal excitability in the central nervous system(1). These receptors probably exist as both homo- and heterodimers that have unique pharmacological and functional properties(2-4). Here we report four cryo-electron microscopy structures of the human mGlu subtypes mGlu2 and mGlu7, including inactive mGlu2 and mGlu7 homodimers; mGlu2 homodimer bound to an agonist and a positive allosteric modulator; and inactive mGlu2-mGlu7 heterodimer. We observed a subtype-dependent dimerization mode for these mGlus, as a unique dimer interface that is mediated by helix IV (and that is important for limiting receptor activity) exists only in the inactive mGlu2 structure. The structures provide molecular details of the inter- and intra-subunit conformational changes that are required for receptor activation, which distinguish class C G-protein-coupled receptors from those in classes A and B. Furthermore, our structure and functional studies of the mGlu2-mGlu7 heterodimer suggest that the mGlu7 subunit has a dominant role in controlling dimeric association and G-protein activation in the heterodimer. These insights into mGlu homo- and heterodimers highlight the complex landscape of mGlu dimerization and activation.
收录类别	SCIE
语种	英语
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000662148600003
出版者	NATURE RESEARCH
原始文献类型	Article; Early Access
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/127515
专题	生命科学与技术学院_特聘教授组_柳红组生命科学与技术学院_特聘教授组_吴蓓丽组
通讯作者	Liu, Hong; Liu, Jianfeng; Sun, Fei; Wu, Beili; Zhao, Qiang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, 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, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou, Peoples R China; 4.Univ Chinese Acad Sci, Beijing, Peoples R China; 5.Chinese Acad Sci, Natl Ctr Prot Sci Beijing, Natl Lab Biomacromol, CAS Ctr Excellence Biomacromol,Inst Biophys, Beijing, Peoples R China; 6.Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Int Res Ctr Sensory Biol & Technol MOST, Key Lab Mol Biophys MOE, Wuhan, Peoples R China; 7.Univ Montpellier, CNRS, INSERM, Inst Genom Fonct IGF, Montpellier, France; 8.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 9.Guangzhou Regenerat Med & Hlth Guangdong Lab, Bioland Lab, Guangzhou, Peoples R China; 10.Chinese Acad Sci, Inst Biophys, Ctr Biol Imaging, Beijing, Peoples R China; 11.Chinese Acad Sci, Zhongshan Branch, Inst Drug Discovery & Dev, Zhongshan, 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	Du, Juan,Wang, Dejian,Fan, Hongcheng,et al. Structures of human mGlu2 and mGlu7 homo- and heterodimers[J]. NATURE,2021,594(7864):589-+.
APA	Du, Juan.,Wang, Dejian.,Fan, Hongcheng.,Xu, Chanjuan.,Tai, Linhua.,...&Zhao, Qiang.(2021).Structures of human mGlu2 and mGlu7 homo- and heterodimers.NATURE,594(7864),589-+.
MLA	Du, Juan,et al."Structures of human mGlu2 and mGlu7 homo- and heterodimers".NATURE 594.7864(2021):589-+.