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Modelling of Fibrillation Induced Selective Cytotoxicity of Phenol Soluble Modulin α3

preprint
submitted on 21.01.2019 and posted on 21.01.2019 by Mitradip Das, Sandeep Dash, B. L. Bhargava
Phenol soluble modulin (PSM) α3, the most toxic member of α-toxin in Staphylococcus aureus bacteria, has been recently found to form cross-α amyloid fibrils and is selectively toxic to the mammalian cell membranes. In this work, it has been discovered that hydrophobic interactions play a major role in fibril formation of PSM-α3 strands, with
stabilization energy of 28.7 kCal/mol. We considered two model bilayers mimicking mammalian and bacterial cell membranes, and found that single α-helix strand penetration is energetically unfavourable in both of them. Hence, we propose a simple model using energetics to understand the reason for selective toxicity of the peptide to the mammalian cell membrane. This study, besides enhancing the understanding of PSM-α3, can also act as a stepping stone in future drug development against ​S. aureus.

History

Email Address of Submitting Author

bhargava@niser.ac.in

Institution

National Institute of Science Education and Research

Country

India

ORCID For Submitting Author

0000-0003-0042-3831

Declaration of Conflict of Interest

The authors declare no conflict of interest.

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