Antimicrobial activity of human prion protein is mediated by its N-terminal region.
(2009) In PLoS ONE 4(10).- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1500533
- author
- Pasupuleti, Mukesh LU ; Roupé, Markus LU ; Rydengård, Victoria LU ; Surewicz, Krystyna ; Surewicz, Witold K ; Chalupka, Anna LU ; Malmsten, Martin LU ; Sørensen, Ole E LU and Schmidtchen, Artur LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 4
- issue
- 10
- article number
- e7358
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000270594000013
- pmid:19809501
- scopus:70350215545
- pmid:19809501
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0007358
- language
- English
- LU publication?
- yes
- id
- f3cbf0d3-76ff-4df3-bd10-2a39e6bd501c (old id 1500533)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/19809501?dopt=Abstract
- date added to LUP
- 2016-04-01 14:48:21
- date last changed
- 2022-03-22 01:57:20
@article{f3cbf0d3-76ff-4df3-bd10-2a39e6bd501c,
abstract = {{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.}},
author = {{Pasupuleti, Mukesh and Roupé, Markus and Rydengård, Victoria and Surewicz, Krystyna and Surewicz, Witold K and Chalupka, Anna and Malmsten, Martin and Sørensen, Ole E and Schmidtchen, Artur}},
issn = {{1932-6203}},
language = {{eng}},
number = {{10}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{Antimicrobial activity of human prion protein is mediated by its N-terminal region.}},
url = {{https://lup.lub.lu.se/search/files/4176066/1508710.pdf}},
doi = {{10.1371/journal.pone.0007358}},
volume = {{4}},
year = {{2009}},
}