Hydrogen/Deuterium Exchange and Molecular Dynamics Analysis of Amyloid Fibrils Formed by a D69K Charge-Pair Mutant of Human Apolipoprotein C-II

Y Mao; CO Zlatic; MDW Griffin; GJ Howlett; N Todorova; I Yarovsky; PR Gooley

Journal article

Hydrogen/Deuterium Exchange and Molecular Dynamics Analysis of Amyloid Fibrils Formed by a D69K Charge-Pair Mutant of Human Apolipoprotein C-II

Y Mao, CO Zlatic, MDW Griffin, GJ Howlett, N Todorova, I Yarovsky, PR Gooley

Biochemistry | Published : 2015

DOI: 10.1021/acs.biochem.5b00535

Abstract

Plasma apolipoproteins form amphipathic α helices in lipid environments but in the lipid-free state show a high propensity to form β structure and self-associate into amyloid fibrils. The widespread occurrence of apolipoproteins in amyloid plaques suggests disease-related roles, specifically in atherosclerosis. To reconcile the dual abilities of apolipoproteins to form either α helices or cross-β sheet structures, we examined fibrils formed by human apolipoprotein C-II (apoC-II). A structural model for apoC-II fibrils shows a cross-β core with parallel β strands, including a buried K30-D69 charge pair. We investigated the effect of abolishing this charge pair in mutant D69K apoC-II. Fluoresc..

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University of Melbourne Researchers

Courtney Zlatic Author

Michael Griffin Author

Paul Gooley Author

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Grants

Awarded by Australian Research Council

Funding Acknowledgements

The Australian Research Council (Project Grants DP0877800 and DP0984565 and Equipment Grant LE120100022) supported this work. M.D.W.G. is the recipient of the C. R. Roper Fellowship and an Australian Research Council Future Fellowship (Project FT140100544). Part of this research was undertaken on the MX-2 beamline of the Australian Synchrotron. This research was undertaken with the assistance of resources from the National Computational Infrastructure (NCI), which is supported by the Australian Government. This research was also supported by Victorian Life Sciences Computation Initiative (VLSCI) Grant VR0028 on its Peak Computing Facility at the University of Melbourne, an initiative of the Victorian Government, Australia.