Structural basis of G s and G i recognition by the human glucagon receptor-Reference-Cited by-同舟云学术

Structural basis of G s and G i recognition by the human glucagon receptor

Published:2020-03-20 Issue:6484 Volume:367 Page:1346-1352
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Qiao Anna¹²³^ORCID,Han Shuo¹²^ORCID,Li Xinmei³⁴^ORCID,Li Zhixin⁵^ORCID,Zhao Peishen⁶^ORCID,Dai Antao¹⁷^ORCID,Chang Rulve⁵^ORCID,Tai Linhua³⁴^ORCID,Tan Qiuxiang¹²^ORCID,Chu Xiaojing¹²^ORCID,Ma Limin¹²^ORCID,Thorsen Thor Seneca⁸^ORCID,Reedtz-Runge Steffen⁸^ORCID,Yang Dehua¹⁷^ORCID,Wang Ming-Wei¹³⁵⁷⁹^ORCID,Sexton Patrick M.⁵⁶^ORCID,Wootten Denise⁵⁶^ORCID,Sun Fei³⁴¹⁰^ORCID,Zhao Qiang²³¹¹^ORCID,Wu Beili¹³⁹¹¹^ORCID

Affiliation:

1. CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

2. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

3. University of Chinese Academy of Sciences, Beijing 100049, China.

4. National Laboratory of Biomacromolecules, National Center of Protein Science–Beijing, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

5. School of Pharmacy, Fudan University, Shanghai 201203, China.

6. Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.

7. National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

8. Novo Nordisk A/S, Måløv 2760, Denmark.

9. School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.

10. Center for Biological Imaging, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

11. CAS Center for Excellence in Biomacromolecules, Chinese Academy of Sciences, Beijing 100101, China.

Abstract

Choosing a partner that fits G protein–coupled receptors (GPCRs) are responsible for transducing diverse signals from outside to inside cells. This process requires specificity both in ligand binding to GPCRs and in coupling between GPCRs and their intracellular partners, G proteins. Qiao et al. determined the structure of the human glucagon receptor (GCGR), a type B GPCR, bound to glucagon and one of two heterotrimeric G proteins, G s or G i1 . GCGR signals mainly through G s , and the structures provide a basis for this specificity. Conformational changes in GCGR, relative to the inactive state, create a binding cavity for the G proteins. The pocket is opened sufficiently to accommodate a bulky binding motif in G s . G i1 can still bind but the pocket does not close around it, so there is a smaller interaction interface. Science , this issue p. 1346

Funder

Shanghai Science and Technology Development Fund

Chinese Academy of Sciences

Ministry of Science and Technology of the People's Republic of China

National Science Foundation of China

Australian national health and medical research council

National Mega R&D Program for Drug Discovery

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference52 articles.