A structural model for apolipoprotein C-II amyloid fibrils: Experimental characterization and molecular dynamics simulations

CL Teoh; CLL Pham; N Todorova; A Hung; CN Lincoln; E Lees; YH Lam; KJ Binger; NH Thomson; SE Radford; TA Smith; SA Müller; A Engel; MDW Griffin; I Yarovsky; PR Gooley; GJ Howlett

Journal article

A structural model for apolipoprotein C-II amyloid fibrils: Experimental characterization and molecular dynamics simulations

CL Teoh, CLL Pham, N Todorova, A Hung, CN Lincoln, E Lees, YH Lam, KJ Binger, NH Thomson, SE Radford, TA Smith, SA Müller, A Engel, MDW Griffin, I Yarovsky, PR Gooley, GJ Howlett

Journal of Molecular Biology | Published : 2011

DOI: 10.1016/j.jmb.2010.12.006

Abstract

The self-assembly of specific proteins to form insoluble amyloid fibrils is a characteristic feature of a number of age-related and debilitating diseases. Lipid-free human apolipoprotein C-II (apoC-II) forms characteristic amyloid fibrils and is one of several apolipoproteins that accumulate in amyloid deposits located within atherosclerotic plaques. X-ray diffraction analysis of aligned apoC-II fibrils indicated a simple cross-β-structure composed of two parallel β-sheets. Examination of apoC-II fibrils using transmission electron microscopy, scanning transmission electron microscopy, and atomic force microscopy indicated that the fibrils are flat ribbons composed of one apoC-II molecule pe..

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University of Melbourne Researchers

Trevor Smith Author

Michael Griffin Author

Paul Gooley Author

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Awarded by Biotechnology and Biological Sciences Research Council

Funding Acknowledgements

We thank Drs. Terry Mulhern, Danny Hatters, and Michael Bailey for discussions and advice throughout the preparation of this work. This work was funded by grants from the Australian Research Council (DP0877800 and DP0984565) and the ARC Center of Excellence in Coherent X-ray Science (CE0561787). We thank Philippe Ringler for STEM. The STEM experiments were supported by the Swiss National Foundation (grant 3100A0-108299 to A.E.) and by the Maurice E. Muller Foundation of Switzerland. Part of this research was undertaken on beamline MX-2 of the Australian Synchrotron.