The Role of Glycation on the Aggregation Properties of IAPP.
amylin
biophysics
diabetes
glycation
protein aggregation
Journal
Frontiers in molecular biosciences
ISSN: 2296-889X
Titre abrégé: Front Mol Biosci
Pays: Switzerland
ID NLM: 101653173
Informations de publication
Date de publication:
2020
2020
Historique:
received:
08
02
2020
accepted:
05
05
2020
entrez:
26
6
2020
pubmed:
26
6
2020
medline:
26
6
2020
Statut:
epublish
Résumé
Epidemiological evidence shows an increased risk for developing Alzheimer's disease in people affected by diabetes, a pathology associated with increased hyperglycemia. A potential factor that could explain this link could be the role that sugars may play in both diseases under the form of glycation. Contrary to glycosylation, glycation is an enzyme-free reaction that leads to formation of toxic advanced glycation end-products (AGEs). In diabetes, the islet amyloid polypeptide (IAPP or amylin) is found to be heavily glycated and to form toxic amyloid-like aggregates, similar to those observed for the Aβ peptides, often also heavily glycated, observed in Alzheimer patients. Here, we studied the effects of glycation on the structure and aggregation properties of IAPP with several biophysical techniques ranging from fluorescence to circular dichroism, mass spectrometry and atomic force microscopy. We demonstrate that glycation occurs exclusively on the N-terminal lysine leaving the only arginine (Arg11) unmodified. At variance with recent studies, we show that the dynamical interplay between glycation and aggregation affects the structure of the peptide, slows down the aggregation process and influences the aggregate morphology.
Identifiants
pubmed: 32582762
doi: 10.3389/fmolb.2020.00104
pmc: PMC7284065
doi:
Types de publication
Journal Article
Langues
eng
Pagination
104Subventions
Organisme : Medical Research Council
ID : MC_PC_13054
Pays : United Kingdom
Informations de copyright
Copyright © 2020 Milordini, Zacco, Percival, Puglisi, Dal Piaz, Temussi and Pastore.
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