Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/105880
Title: Antimicrobial effects of helix D-derived peptides of human antithrombin III
Authors: Papareddy, Praveen
Kalle, Martina
Bhongir, Ravi KV
Mӧrgelin, Matthias
Malmsten, Martin
Schmidtchen, Artur
Keywords: DRNTU::Science::Biological sciences::Human anatomy and physiology
Issue Date: 2014
Source: Papareddy, P., Kalle, M., Bhongir, R. K., Morgelin, M., Malmsten, M., & Schmidtchen, A. (2014). Antimicrobial effects of helix D-derived peptides of human antithrombin III. Journal of biological chemistry, 1-14.
Series/Report no.: Journal of biological chemistry
Abstract: Antithrombin III (ATIII) is a key antiproteinase involved in blood coagulation. Previous investigations have shown that ATIII is degraded by Staphylococcus aureus V8 protease, leading to release of heparin binding fragments derived from its D helix. As heparin binding and antimicrobial activity of peptides frequently overlap, we here set out to explore possible antibacterial effects of intact and degraded ATIII. In contrast to intact ATIII, the results showed that extensive degradation of the molecule yielded fragments with antimicrobial activity. Correspondingly, the heparin-binding, helix D-derived, peptide FFFAKLNCRL-YRKANKSSKLV (FFF21) of human ATIII, was found to be antimicrobial against particularly the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa. Fluorescence microscopy and electron microscopy studies demonstrated that FFF21 binds to, and permeabilizes, bacterial membranes. Analogously, FFF21 was found to induce membrane leakage of model anionic liposomes. In vivo, FFF21 significantly reduced P. aeruginosa infection in mice. Additionally, FFF21 displayed anti-endotoxic effects in vitro. Taken together, our results suggest novel roles for ATIII-derived peptide fragments in host defense.
URI: https://hdl.handle.net/10356/105880
http://hdl.handle.net/10220/20949
ISSN: 0021-9258
DOI: 10.1074/jbc.M114.570465
Rights: © 2014 The American Society for Biochemistry and Molecular Biology. This is the author created version of a work that has been peer reviewed and accepted for publication by Journal of Biological Chemistry, The American Society for Biochemistry and Molecular Biology. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1074/jbc.M114.570465].
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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