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Antimicrobial activity of human prion protein is mediated by its N-terminal region
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2009 (English)In: PloS one, ISSN 1932-6203, Vol. 4, no 10, e7358- p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Cellular prion-related protein (PrP(c)) is a cell-surface protein that is ubiquitously expressed in the human body. The multifunctionality of PrP(c), and presence of an exposed cationic and heparin-binding N-terminus, a feature characterizing many antimicrobial peptides, made us hypothesize that PrP(c) could exert antimicrobial activity. METHODOLOGY AND PRINCIPAL FINDINGS: Intact recombinant PrP exerted antibacterial and antifungal effects at normal and low pH. Studies employing recombinant PrP and N- and C-terminally truncated variants, as well as overlapping peptide 20mers, demonstrated that the antimicrobial activity is mediated by the unstructured N-terminal part of the protein. Synthetic peptides of the N-terminus of PrP killed the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, and the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen after treatment with the "classical" human antimicrobial peptide LL-37. In contrast to LL-37, however, no marked helix induction was detected for the PrP-derived peptides in presence of negatively charged (bacteria-mimicking) liposomes. PrP furthermore showed an inducible expression during wounding of human skin ex vivo and in vivo, as well as stimulation of keratinocytes with TGF-alpha in vitro. CONCLUSIONS: The demonstration of an antimicrobial activity of PrP, localisation of its activity to the N-terminal and heparin-binding region, combined with results showing an increased expression of PrP during wounding, indicate that PrPs could have a previously undisclosed role in host defense.

Place, publisher, year, edition, pages
2009. Vol. 4, no 10, e7358- p.
National Category
Medical and Health Sciences Pharmaceutical Sciences
URN: urn:nbn:se:uu:diva-109438DOI: 10.1371/journal.pone.0007358ISI: 000270594000013PubMedID: 19809501OAI: oai:DiVA.org:uu-109438DiVA: diva2:272456
Available from: 2009-10-15 Created: 2009-10-15 Last updated: 2010-11-09Bibliographically approved

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