MC4R biased signalling and the conformational basis of biological function selections.
Biased signalling
Conformational studies
MC4R
MC4R drug design
MC4R structure
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
revised:
26
05
2022
received:
11
11
2021
accepted:
01
06
2022
pubmed:
13
7
2022
medline:
4
8
2022
entrez:
12
7
2022
Statut:
ppublish
Résumé
The MC4R, a GPCR, has long been a major target for obesity treatment. As the most well-studied melanocortin receptor subtype, the evolutionary knowledge pushes the drug development and structure-activity relationship (SAR) moving forward. The past decades have witnessed the evolution of scientists' view on GPCRs gradually from the control of a single canonical signalling pathway via a bilateral 'active-inactive' model to a multi-state alternative model where the ligands' binding affects the selection of the downstream signalling. This evolution brings the concept of biased signalling and the beginning of the next generation of peptide drug development, with the aim of turning from receptor subtype specificity to signalling pathway selectivity. The determination of the value structures of the MC4R revealed insights into the working mechanism of MC4R activation upon binding of agonists. However, new challenge has risen as we seek to unravel the mystery of MC4R signalling selection. Thus, more biased agonists and ligands with representative biological functions are needed to solve the rest of the puzzle.
Identifiants
pubmed: 35818295
doi: 10.1111/jcmm.17441
pmc: PMC9344818
doi:
Substances chimiques
Ligands
0
Peptides
0
Receptor, Melanocortin, Type 4
0
Receptors, Melanocortin
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
4125-4136Informations de copyright
© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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