Structural basis of GABAB receptor-Gi protein coupling

被引：63

作者：

Shen, Cangsong ^{[1
,2
,3
,4
]}

Mao, Chunyou ^{[2
,3
,4
,5
]}

Xu, Chanjuan ^{[1
,6
]}

Jin, Nan ^{[1
,2
,3
,4
]}

Zhang, Huibing ^{[2
,3
,4
,5
]}

Shen, Dan-Dan ^{[2
,3
,4
,5
]}

Shen, Qingya ^{[2
,3
,4
,5
]}

Wang, Xiaomei ^{[1
]}

Hou, Tingjun ^{[7
]}

Chen, Zhong ^{[8
]}

Rondard, Philippe ^{[9
]}

Pin, Jean-Philippe ^{[9
]}

Zhang, Yan ^{[2
,3
,4
,5
,10
]}

Liu, Jianfeng ^{[1
,6
]}

机构：

[1] Huazhong Univ Sci & Technol HUST, Int Res Ctr Sensory Biol & Technol MOST, Coll Life Sci & Technol, ZJU HUST Joint Lab Cellular Signaling,Key Lab Mol, Wuhan, Peoples R China

[2] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Biophys, Hangzhou, Peoples R China

[3] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Pathol, Hangzhou, Peoples R China

[4] Zhejiang Univ, Med Ctr, Liangzhu Lab, Hangzhou, Peoples R China

[5] Zhejiang Prov Key Lab Immun & Inflammatory Dis, Hangzhou, Peoples R China

[6] Guangzhou Regenerat Med & Hlth Guangdong Lab, Bioland Lab, Guangzhou, Peoples R China

[7] Zhejiang Univ, Coll Pharmaceut Sci, Innovat Inst Artificial Intelligence Med, Hangzhou, Peoples R China

[8] Zhejiang Chinese Med Univ, Key Lab Neuropharmacol & Translat Med Zhejiang P, Hangzhou, Peoples R China

[9] Univ Montpellier, CNRS, INSERM, Inst Genom Fonct, F-34094 Montpellier, France

[10] Zhejiang Univ, MOE Frontier Sci Ctr Brain Res & Brain Machine In, Sch Med, Hangzhou, Peoples R China

来源：

NATURE | 2021年 / 594卷 / 7864期

基金：

中国国家自然科学基金;

关键词：

CRYO-EM STRUCTURE; 2ND INTRACELLULAR LOOP; ACTIVATION; SUBUNIT; VISUALIZATION; RECOGNITION; SYSTEM; GB2;

D O I：

10.1038/s41586-021-03507-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

G-protein-coupled receptors (GPCRs) have central roles in intercellular communication(1,2). Structural studies have revealed how GPCRs can activate G proteins. However, whether this mechanism is conserved among all classes of GPCR remains unknown. Here we report the structure of the class-C heterodimeric GABA(B) receptor, which is activated by the inhibitory transmitter GABA, in its active form complexed with G(i1) protein. We found that a single G protein interacts with the GB2 subunit of the GABA(B) receptor at a site that mainly involves intracellular loop 2 on the side of the transmembrane domain. This is in contrast to the G protein binding in a central cavity, as has been observed with other classes of GPCR. This binding mode results from the active form of the transmembrane domain of this GABA(B) receptor being different from that of other GPCRs, as it shows no outside movement of transmembrane helix 6. Our work also provides details of the inter- and intra-subunit changes that link agonist binding to G-protein activation in this heterodimeric complex.

引用

页码：594 / +

页数：17

共 46 条

[1] PHENIX: a comprehensive Python']Python-based system for macromolecular structure solution [J].