Activation pathway of a G protein-coupled receptor uncovers conformational intermediates as targets for allosteric drug design

Shaoyong Lu; Xinheng He; Zhao Yang; Zongtao Chai; Shuhua Zhou; Junyan Wang; Ashfaq Ur Rehman; Duan Ni; Jun Pu; Jinpeng Sun; Jian Zhang

doi:10.1038/s41467-021-25020-9

Nature Communications (Aug 2021)

Activation pathway of a G protein-coupled receptor uncovers conformational intermediates as targets for allosteric drug design

Shaoyong Lu,
Xinheng He,
Zhao Yang,
Zongtao Chai,
Shuhua Zhou,
Junyan Wang,
Ashfaq Ur Rehman,
Duan Ni,
Jun Pu,
Jinpeng Sun,
Jian Zhang

Affiliations

Shaoyong Lu: College of Pharmacy, Ningxia Medical University
Xinheng He: The CAS Key Laboratory of Receptor Research, Shanghai Institute of Material Medica, Chinese Academy of Sciences
Zhao Yang: Department of Biochemistry and Molecular Biology, Key Laboratory Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University
Zongtao Chai: Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
Shuhua Zhou: Department of Biochemistry and Molecular Biology, Key Laboratory Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University
Junyan Wang: Department of Biochemistry and Molecular Biology, Key Laboratory Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University
Ashfaq Ur Rehman: State Key Laboratory of Oncogenes and Related Genes, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University, School of Medicine
Duan Ni: State Key Laboratory of Oncogenes and Related Genes, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University, School of Medicine
Jun Pu: Department of Cardiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine
Jinpeng Sun: Department of Biochemistry and Molecular Biology, Key Laboratory Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University
Jian Zhang: College of Pharmacy, Ningxia Medical University

DOI: https://doi.org/10.1038/s41467-021-25020-9
Journal volume & issue: Vol. 12, no. 1
pp. 1 – 15

Abstract

Read online

G protein-coupled receptors (GPCRs) are a critical target in modern drug development across a wide range of indications. Here the authors provide a comprehensive characterization of a typical GPCR, the angiotensin II (AngII) type 1 receptor (AT1R), and provide insight into its activation mechanism that suggest avenues for the design of allosteric GPCR modulators.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

About the journal