Structures of G(i)-bound metabotropic glutamate receptors mGlu2 and mGlu4

doi:10.1038/s41586-021-03495-2

	Structures of G(i)-bound metabotropic glutamate receptors mGlu2 and mGlu4
	Lin, Shuling 1,2; Han, Shuo 3; Cai, Xiaoqing 1,4; Tan, Qiuxiang 1; Zhou, Kexiu1,2,5 ; Wang, Dejian 2,3; Wang, Xinwei 1,2; Du, Juan 6; Yi, Cuiying ; Chu, Xiaojing 1; Dai, Antao 1,4; Zhou, Yan 1,3,4; Chen, Yan 3,7; Zhou, Yu 2; Liu, Hong 2; Liu, Jianfeng 8; Yang, Dehua 1,2,4,9; Wang, Ming-Wei1,2,4,5,7,10 ; Zhao, Qiang 2,3,11; Wu, Beili1,2,5,6
	2021-06-24
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:583-+
DOI	10.1038/s41586-021-03495-2
摘要	The metabotropic glutamate receptors (mGlus) have key roles in modulating cell excitability and synaptic transmission in response to glutamate (the main excitatory neurotransmitter in the central nervous system)(1). It has previously been suggested that only one receptor subunit within an mGlu homodimer is responsible for coupling to G protein during receptor activation(2). However, the molecular mechanism that underlies the asymmetric signalling of mGlus remains unknown. Here we report two cryo-electron microscopy structures of human mGlu2 and mGlu4 bound to heterotrimeric G(i) protein. The structures reveal a G-protein-binding site formed by three intracellular loops and helices III and IV that is distinct from the corresponding binding site in all of the other G-protein-coupled receptor (GPCR) structures. Furthermore, we observed an asymmetric dimer interface of the transmembrane domain of the receptor in the two mGlu-G(i) structures. We confirmed that the asymmetric dimerization is crucial for receptor activation, which was supported by functional data; this dimerization may provide a molecular basis for the asymmetric signal transduction of mGlus. These findings offer insights into receptor signalling of class C GPCRs.
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:000665247800023
出版者	NATURE RESEARCH
原始文献类型	Article
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/127866
专题	生命科学与技术学院_博士生生命科学与技术学院_特聘教授组_王明伟组生命科学与技术学院_特聘教授组_吴蓓丽组
通讯作者	Wang, Ming-Wei; Zhao, Qiang; Wu, Beili
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China; 2.Univ Chinese Acad Sci, Beijing, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China; 4.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai, Peoples R China; 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 6.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou, Peoples R China; 7.Fudan Univ, Sch Pharm, Shanghai, Peoples R China; 8.Huazhong Univ Sci & Technol, Int Res Ctr Sensory Biol & Technol MOST, Coll Life Sci & Technol, Key Lab Mol Biophys MOE, Wuhan, Peoples R China; 9.Guangzhou Regenerat Med & Hlth Guangdong Lab, Bioland Lab, Guangzhou, Peoples R China; 10.Fudan Univ, Sch Basic Med Sci, Shanghai, Peoples R China; 11.Chinese Acad Sci, Inst Drug Discovery & Dev, Zhongshan Branch, 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	Lin, Shuling,Han, Shuo,Cai, Xiaoqing,et al. Structures of G(i)-bound metabotropic glutamate receptors mGlu2 and mGlu4[J]. NATURE,2021,594(7864):583-+.
APA	Lin, Shuling.,Han, Shuo.,Cai, Xiaoqing.,Tan, Qiuxiang.,Zhou, Kexiu.,...&Wu, Beili.(2021).Structures of G(i)-bound metabotropic glutamate receptors mGlu2 and mGlu4.NATURE,594(7864),583-+.
MLA	Lin, Shuling,et al."Structures of G(i)-bound metabotropic glutamate receptors mGlu2 and mGlu4".NATURE 594.7864(2021):583-+.