Nature Communications (Jan 2022)
Dynamics of GLP-1R peptide agonist engagement are correlated with kinetics of G protein activation
- Giuseppe Deganutti,
- Yi-Lynn Liang,
- Xin Zhang,
- Maryam Khoshouei,
- Lachlan Clydesdale,
- Matthew J. Belousoff,
- Hari Venugopal,
- Tin T. Truong,
- Alisa Glukhova,
- Andrew N. Keller,
- Karen J. Gregory,
- Katie Leach,
- Arthur Christopoulos,
- Radostin Danev,
- Christopher A. Reynolds,
- Peishen Zhao,
- Patrick M. Sexton,
- Denise Wootten
Affiliations
- Giuseppe Deganutti
- Centre for Sport, Exercise and Life Sciences, Coventry University
- Yi-Lynn Liang
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University
- Xin Zhang
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University
- Maryam Khoshouei
- Department of Molecular Structural Biology, Max Planck Institute of Biochemistry
- Lachlan Clydesdale
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University
- Matthew J. Belousoff
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University
- Hari Venugopal
- Ramaciotti Centre for Cryo-Electron Microscopy, Monash University
- Tin T. Truong
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University
- Alisa Glukhova
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University
- Andrew N. Keller
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University
- Karen J. Gregory
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University
- Katie Leach
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University
- Arthur Christopoulos
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University
- Radostin Danev
- Graduate School of Medicine, University of Tokyo
- Christopher A. Reynolds
- Centre for Sport, Exercise and Life Sciences, Coventry University
- Peishen Zhao
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University
- Patrick M. Sexton
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University
- Denise Wootten
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University
- DOI
- https://doi.org/10.1038/s41467-021-27760-0
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 18
Abstract
The glucagon-like peptide-1 receptor (GLP-1R) can be targeted in the treatment of diabetes, obesity and other metabolic disorders. Here, the authors assess the molecular mechanisms of peptide agonists binding to GLP-1R and the responses elucidated by these ligands, including distinct kinetics of G protein activation.
