A viral insulin-like peptide is a natural competitive antagonist of the human IGF-1 receptor.
IGF-1
Insulin
Insulin-like growth factor 1
Peptide synthesis
Receptor antagonism
Virus-derived peptides
Journal
Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
11
04
2021
revised:
03
08
2021
accepted:
10
08
2021
pubmed:
18
8
2021
medline:
24
3
2022
entrez:
17
8
2021
Statut:
ppublish
Résumé
Natural sources of molecular diversity remain of utmost importance as a reservoir of proteins and peptides with unique biological functions. We recently identified such a family of viral insulin-like peptides (VILPs). We sought to advance the chemical methods in synthesis to explore the structure-function relationship within these VILPs, and the molecular basis for differential biological activities relative to human IGF-1 and insulin. Optimized chemical methods in synthesis were established for a set of VILPs and related analogs. These modified forms included the substitution of select VILP chains with those derived from human insulin and IGF-1. Each peptide was assessed in vitro for agonism and antagonism at the human insulin and the human insulin-like growth factor 1 receptor (IGF-1R). We report here that one of these VILPs, lymphocystis disease virus-1 (LCDV1)-VILP, has the unique property to be a potent and full antagonist of the IGF-1R. We demonstrate the coordinated importance of the B- and C-chains of the VILP in regulating this activity. Moreover, mutation of the glycine following the first cysteine in the B-chain of IGF-1 to serine, in concert with substitution to the connecting peptide of LCDV1-VILP, converted native IGF-1 to a high potency antagonist. The results reveal novel aspects in ligand-receptor interactions at the IGF-1 receptor and identify a set of antagonists of potential medicinal importance.
Identifiants
pubmed: 34400347
pii: S2212-8778(21)00163-0
doi: 10.1016/j.molmet.2021.101316
pmc: PMC8621328
pii:
doi:
Substances chimiques
IGF1R protein, human
0
Neuropeptides
0
insulin-related neuropeptide
0
Receptor, IGF Type 1
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
101316Subventions
Organisme : NIDDK NIH HHS
ID : K01 DK117967
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK036836
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK031036
Pays : United States
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier GmbH.. All rights reserved.
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