title: Effects of oxidation, pH and lipids on amyloidogenic peptide structure: implications for fibril formation?
abstract: We have performed experimental and computational studies to investigate the influences of phospholipids, methionine oxidation and acidic pH on amyloid fibril formation by a peptide derived from human apolipoprotein C-II (apoC-II), a known component of proteinaceous atherosclerotic plaques. Fibril growth monitored by thioflavin T fluorescence revealed inhibition under lipid-rich and oxidising conditions. We subsequently performed fully-solvated atomistic molecular dynamics (MD) simulations of the peptide monomer to study its conformations under both fibril favouring (neutral and low pH) and inhibiting (lipid-rich and oxidising) conditions. Examination of the chain topology, backbone hydrogen-bonding patterns and aromatic sidechain orientations of the peptide under different conditions reveals that, while the peptide adopts similar structures under the fibril-favouring conditions, significantly different structures are obtained under fibril-disruptive conditions. Based on our results, we advance hypotheses for the roles of peptide conformation on aggregation and fibrillisation propensities.
authors.affiliation: School of Applied Sciences, RMIT University, GPO Box 2476V, Melbourne, VIC 3001, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hung
authors.forename: Michael D W
authors.initials: MD
authors.lastname: Griffin
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Howlett
authors.forename: Irene
authors.initials: I
authors.lastname: Yarovsky