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Phase transitions and structure analysis in wild-type, A30P, E46K, and A53T mutants of α-synuclein

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Abstract

α-Synuclein has been implicated in the development of neural plaques in Parkinson’s Disease and Lewy-Body Dementia. This paper reports on the structural phase change behavior exhibited over a relevant range of temperatures in canonical protein Monte Carlo simulations for wild-type α-synuclein and three of its familial variants. We performed and analyzed these simulations to determine residue occupancy variations above and below this phase transition. From this analysis, we found regions above the phase transition temperature that consistently exhibited increased propensity for formation of long-chain beta-sheets, suggesting a possible role in α-synuclein aggregation.

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Acknowledgments

This research was supported by a grant from Alberta Innovates Health Solutions under the CRIO program. J. A. T acknowledges funding from NSERC (Canada).

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Authors and Affiliations

  1. Department of Physics, University of Alberta, Edmonton, AB, T6G2E1, Canada

    Mark A. Healey, Michael T. Woodside & Jack A. Tuszynski

  2. National Institute for Nanotechnology, National Research Council, Edmonton, AB, T6G2M9, Canada

    Michael T. Woodside

  3. Department of Oncology, University of Alberta, Edmonton, AB, T6G1Z2, Canada

    Jack A. Tuszynski

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  1. Mark A. Healey
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Correspondence to Jack A. Tuszynski.

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Healey, M.A., Woodside, M.T. & Tuszynski, J.A. Phase transitions and structure analysis in wild-type, A30P, E46K, and A53T mutants of α-synuclein. Eur Biophys J 45, 355–364 (2016). https://doi.org/10.1007/s00249-015-1103-0

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  • DOI: https://doi.org/10.1007/s00249-015-1103-0

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