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    Specific refolding pathway of viscumin A chain in membrane-like medium reveals a possible mechanism of toxin entry into cell

    Volynsky, P.E. and Nolde, D.E. and Zakharova, G.S. and Palmer, Rex A. and Tonevitsky, A.G. and Efremov, R.G. (2019) Specific refolding pathway of viscumin A chain in membrane-like medium reveals a possible mechanism of toxin entry into cell. Scientific Reports 9 (1), p. 413. ISSN 2045-2322.

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    Abstract

    How is a water-soluble globular protein able to spontaneously cross a cellular membrane? It is commonly accepted that it undergoes significant structural rearrangements on the lipid-water interface, thus acquiring membrane binding and penetration ability. In this study molecular dynamics (MD) simulations have been used to explore large-scale conformational changes of the globular viscumin A chain in a complex environment - comprising urea and chloroform/methanol (CHCl /MeOH) mixture. Being well-packed in aqueous solution, viscumin A undergoes global structural rearrangements in both organic media. In urea, the protein is "swelling" and gradually loses its long-distance contacts, thus resembling the "molten globule" state. In CHCl /MeOH, viscumin A is in effect turned "inside out". This is accompanied with strengthening of the secondary structure and surface exposure of hydrophobic epitopes originally buried inside the globule. Resulting solvent-adapted models were further subjected to Monte Carlo simulations with an implicit hydrophobic slab membrane. In contrast to only a few point surface contacts in water and two short regions with weak protein-lipid interactions in urea, MD-derived structures in CHCl /MeOH reveal multiple determinants of membrane interaction. Consequently it is now possible to propose a specific pathway for the structural adaptation of viscumin A with respect to the cell membrane - a probable first step of its translocation into cytoplasmic targets.

    Metadata

    Item Type: Article
    School: Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
    SWORD Depositor: Mr Joe Tenant
    Depositing User: Mr Joe Tenant
    Date Deposited: 05 Mar 2019 15:02
    Last Modified: 02 Aug 2023 17:48
    URI: https://eprints.bbk.ac.uk/id/eprint/26142

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