Coarse-grained MD simulations reveal beta-amyloid fibrils of various sizes bind to interfacial liquid-ordered and liquid-disordered regions in phase separated lipid rafts with diverse membrane-bound conformational states.
Amyloid fibrils membrane interactions
Coarse-grained model
Lipid rafts
MD simulations
Oxidized cholesterols
Phase-separated lipid domains
Journal
Biophysical chemistry
ISSN: 1873-4200
Titre abrégé: Biophys Chem
Pays: Netherlands
ID NLM: 0403171
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
20
12
2019
revised:
23
02
2020
accepted:
29
02
2020
pubmed:
18
3
2020
medline:
31
3
2021
entrez:
18
3
2020
Statut:
ppublish
Résumé
The membrane binding behaviors of beta-amyloid fibrils, dimers to pentamers, from solution to lipid raft surfaces, were investigated using coarse-grained (CG) MD simulations. Our CG rafts contain phospholipid, cholesterol (with or without tail- or headgroup modifications), and with or without asymmetrically distributed monosialotetrahexosylganglioside (GM1). All rafts exhibited liquid-ordered (Lo), liquid-disordered (Ld), and interfacial Lo/Ld (Lod) domains, with domain sizes depending on cholesterol structure. For rafts without GM1, all fibrils bound to the Lod domains. Specifically, dimer fibrils bound exclusively via the C-terminal, while larger fibrils could bind via other protein regions. Interestingly, a membrane-inserted state was detected for a trimer fibril in a raft with tail-group modified cholesterol. For rafts containing GM1, fibrils bound either to the GM1-clusters, with numerous membrane-bound conformations, or to the non-GM1-containing-Lod domains via the C-terminal. Our results indicate beta-amyloid fibrils bind to Lod domains or GM1, with diversified membrane-bound conformations, in structurally heterogeneous lipid membranes.
Identifiants
pubmed: 32179374
pii: S0301-4622(20)30063-6
doi: 10.1016/j.bpc.2020.106355
pmc: PMC7254575
mid: NIHMS1587710
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Lipids
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
106355Subventions
Organisme : NIGMS NIH HHS
ID : RC1 GM090897
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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