{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["6(4)"],"submitter":["Tofoleanu F"],"pubmed_abstract":["Fibrillar aggregates of misfolded amyloid proteins are involved in a variety of diseases such as Alzheimer disease (AD), type 2 diabetes, Parkinson, Huntington and prion-related diseases. In the case of AD amyloid ? (A?) peptides, the toxicity of amyloid oligomers and larger fibrillar aggregates is related to perturbing the biological function of the adjacent cellular membrane. We used atomistic molecular dynamics (MD) simulations of A? 9-40 fibrillar oligomers modeled as protofilament segments, including lipid bilayers and explicit water molecules, to probe the first steps in the mechanism of A?-membrane interactions. Our study identified the electrostatic interaction between charged peptide residues and the lipid headgroups as the principal driving force that can modulate the further penetration of the C-termini of amyloid fibrils or fibrillar oligomers into the hydrophobic region of lipid membranes. These findings advance our understanding of the detailed molecular mechanisms and the effects related to A?-membrane interactions, and suggest a polymorphic structural character of amyloid ion channels embedded in lipid bilayers. While inter-peptide hydrogen bonds leading to the formation of ?-strands may still play a stabilizing role in amyloid channel structures, these may also present a significant helical content in peptide regions (e.g., termini) that are subject to direct interactions with lipids rather than with neighboring A? peptides."],"journal":["Prion"],"pagination":["339-45"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3609060"],"repository":["biostudies-literature"],"pubmed_title":["Alzheimer A? peptide interactions with lipid membranes: fibrils, oligomers and polymorphic amyloid channels."],"pmcid":["PMC3609060"],"pubmed_authors":["Buchete NV","Tofoleanu F"],"additional_accession":[]},"is_claimable":false,"name":"Alzheimer A? peptide interactions with lipid membranes: fibrils, oligomers and polymorphic amyloid channels.","description":"Fibrillar aggregates of misfolded amyloid proteins are involved in a variety of diseases such as Alzheimer disease (AD), type 2 diabetes, Parkinson, Huntington and prion-related diseases. In the case of AD amyloid ? (A?) peptides, the toxicity of amyloid oligomers and larger fibrillar aggregates is related to perturbing the biological function of the adjacent cellular membrane. We used atomistic molecular dynamics (MD) simulations of A? 9-40 fibrillar oligomers modeled as protofilament segments, including lipid bilayers and explicit water molecules, to probe the first steps in the mechanism of A?-membrane interactions. Our study identified the electrostatic interaction between charged peptide residues and the lipid headgroups as the principal driving force that can modulate the further penetration of the C-termini of amyloid fibrils or fibrillar oligomers into the hydrophobic region of lipid membranes. These findings advance our understanding of the detailed molecular mechanisms and the effects related to A?-membrane interactions, and suggest a polymorphic structural character of amyloid ion channels embedded in lipid bilayers. While inter-peptide hydrogen bonds leading to the formation of ?-strands may still play a stabilizing role in amyloid channel structures, these may also present a significant helical content in peptide regions (e.g., termini) that are subject to direct interactions with lipids rather than with neighboring A? peptides.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Sep-Oct","modification":"2021-02-19T18:29:54Z","creation":"2019-03-27T01:06:39Z"},"accession":"S-EPMC3609060","cross_references":{"pubmed":["22874669"],"doi":["10.4161/pri.21022"]}}