Differences in Medium-Induced Conformational Plasticity Presumably Underlie Different Cytotoxic Activity of Ricin and Viscumin

Pavel Volynsky, Diana Maltseva, Valentin Tabakmakher, Eduard V. Bocharov, Maria Raygorodskaya, Galina Zakharova, Elena Britikova, Alexander Tonevitsky, Roman Efremov

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1 Scopus citations


Structurally similar catalytic subunits A of ricin (RTA) and viscumin (MLA) exhibit cytotoxic activity through ribosome inactivation. Ricin is more cytotoxic than viscumin, although the molecular mechanisms behind this difference are still poorly understood. To shed more light on this problem, we used a combined biochemical/molecular modeling approach to assess possible relationships between the activity of toxins and their structural/dynamic properties. Based on bioassay measurements, it was suggested that the differences in activity are associated with the ability of RTA and MLA to undergo structural/hydrophobic rearrangements during trafficking through the endoplasmic reticulum (ER) membrane. Molecular dynamics simulations and surface hydrophobicity mapping of both proteins in different media showed that RTA rearranges its structure in a membrane-like environment much more efficiently than MLA. Their refolded states also drastically differ in terms of hydrophobic organization. We assume that the higher conformational plasticity of RTA is favorable for the ER-mediated translocation pathway, which leads to a higher rate of toxin penetration into the cytoplasm.

Original languageEnglish
Article number295
Issue number2
StatePublished - 11 Feb 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


Funding: MD simulations, proteins’ isolation and characterization, cell culturing works, and hydrophobicity mapping of protein surfaces were supported by the Russian Foundation for Basic Research (projects #20-04-00697, #20-54-81015). MC calculations with the implicit membrane model were supported by the Russian Science Foundation (project #18-14-00375). Molecular biology experiments and supercomputer calculations were performed within the framework of the HSE University Basic Research Program.

FundersFunder number
Russian Foundation for Basic Research20-04-00697, 20-54-81015
Russian Science Foundation18-14-00375


    • Medium effects on protein structure
    • Membrane trafficking of proteins
    • Molecular dynamics
    • Protein–membrane interactions
    • Type II ribosome inactivating proteins


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