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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