Lipid-Chaperone Hypothesis: A Common Molecular Mechanism of Membrane Disruption by Intrinsically Disordered Proteins.
Alzheimer
Intrinsically disordered proteins
Parkinson
diabetes mellitus
lipid-chaperone hypothesis
oxidized lipids
Journal
ACS chemical neuroscience
ISSN: 1948-7193
Titre abrégé: ACS Chem Neurosci
Pays: United States
ID NLM: 101525337
Informations de publication
Date de publication:
16 12 2020
16 12 2020
Historique:
pubmed:
4
12
2020
medline:
22
6
2021
entrez:
3
12
2020
Statut:
ppublish
Résumé
An increasing number of human diseases has been shown to be linked to aggregation and amyloid formation by intrinsically disordered proteins (IDPs). Amylin, amyloid-β, and α-synuclein are, indeed, involved in type-II diabetes, Alzheimer's, and Parkinson's, respectively. Despite the correlation of the toxicity of these proteins at early aggregation stages with membrane damage, the molecular events underlying the process is quite complex to understand. In this study, we demonstrate the crucial role of free lipids in the formation of lipid-protein complex, which enables an easy membrane insertion for amylin, amyloid-β, and α-synuclein. Experimental results from a variety of biophysical methods and molecular dynamics results reveal that this common molecular pathway in membrane poration is shared by amyloidogenic (amylin, amyloid-β, and α-synuclein) and nonamyloidogenic (rat IAPP, β-synuclein) proteins. Based on these results, we propose a "lipid-chaperone" hypothesis as a unifying framework for protein-membrane poration.
Identifiants
pubmed: 33269918
doi: 10.1021/acschemneuro.0c00588
pmc: PMC7769131
mid: NIHMS1655055
doi:
Substances chimiques
Amyloid
0
Amyloidogenic Proteins
0
Intrinsically Disordered Proteins
0
Islet Amyloid Polypeptide
0
Lipids
0
alpha-Synuclein
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4336-4350Subventions
Organisme : NIA NIH HHS
ID : R01 AG048934
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA HL001055
Pays : United States
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