Nature Communications (Feb 2022)
Structural insights into multiplexed pharmacological actions of tirzepatide and peptide 20 at the GIP, GLP-1 or glucagon receptors
- Fenghui Zhao,
- Qingtong Zhou,
- Zhaotong Cong,
- Kaini Hang,
- Xinyu Zou,
- Chao Zhang,
- Yan Chen,
- Antao Dai,
- Anyi Liang,
- Qianqian Ming,
- Mu Wang,
- Li-Nan Chen,
- Peiyu Xu,
- Rulve Chang,
- Wenbo Feng,
- Tian Xia,
- Yan Zhang,
- Beili Wu,
- Dehua Yang,
- Lihua Zhao,
- H. Eric Xu,
- Ming-Wei Wang
Affiliations
- Fenghui Zhao
- School of Pharmacy, Fudan University
- Qingtong Zhou
- Department of Pharmacology, School of Basic Medical Sciences, Fudan University
- Zhaotong Cong
- Department of Pharmacology, School of Basic Medical Sciences, Fudan University
- Kaini Hang
- School of Life Science and Technology, ShanghaiTech University
- Xinyu Zou
- School of Artificial Intelligence and Automation, Huazhong University of Science and Technology
- Chao Zhang
- School of Life Science and Technology, ShanghaiTech University
- Yan Chen
- Department of Pharmacology, School of Basic Medical Sciences, Fudan University
- Antao Dai
- The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- Anyi Liang
- School of Artificial Intelligence and Automation, Huazhong University of Science and Technology
- Qianqian Ming
- Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
- Mu Wang
- School of Life Science and Technology, ShanghaiTech University
- Li-Nan Chen
- Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
- Peiyu Xu
- The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- Rulve Chang
- School of Pharmacy, Fudan University
- Wenbo Feng
- Department of Pharmacology, School of Basic Medical Sciences, Fudan University
- Tian Xia
- School of Artificial Intelligence and Automation, Huazhong University of Science and Technology
- Yan Zhang
- Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
- Beili Wu
- The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- Dehua Yang
- The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- Lihua Zhao
- The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- H. Eric Xu
- The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- Ming-Wei Wang
- School of Pharmacy, Fudan University
- DOI
- https://doi.org/10.1038/s41467-022-28683-0
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 16
Abstract
Multi-targeting agonists at GIPR, GLP-1R or GCGR are pursued vigorously. Here, the authors report cryo-EM structures of tirzepatide-bound GIPR and GLP-1R, peptide 20-bound GIPR, GLP-1R and GCGR, revealing the molecular basis of their multiplexed pharmacological actions.
