Journal article

Effects of oxidation, pH and lipids on amyloidogenic peptide structure: implications for fibril formation?

Andrew Hung, Michael DW Griffin, Geoffrey J Howlett, Irene Yarovsky

EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS | SPRINGER | Published : 2008

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-..

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Grants

Funding Acknowledgements

We acknowledge the Australian Partnership for Advanced Computing (APAC) and Victorian Partnership for Advanced Computing (VPAC) for provision of computational resources, and the latter for provision of funds under the eResearch grants scheme. We also thank our colleagues at RMIT University (Sue Legge, Nevena Todorova and Akin Budi) for many helpful discussions.