Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, Lund, Sweden.
PLoS One. 2009 Oct 7;4(10):e7358. doi: 10.1371/journal.pone.0007358.
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.
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.
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.
细胞朊蛋白相关蛋白（PrP(c)）是一种广泛表达于人体的细胞表面蛋白。PrP(c)的多功能性，以及暴露的阳离子和肝素结合的 N 端的存在，是许多抗菌肽的特征，这使我们假设 PrP(c)可能具有抗菌活性。
完整的重组 PrP 在正常和低 pH 值下表现出抗菌和抗真菌作用。使用重组 PrP 及其 N 和 C 端截断变体以及重叠肽 20 mers 的研究表明，抗菌活性是由蛋白质的无规卷曲 N 端介导的。PrP 的 N 端合成肽可杀死革兰氏阴性菌大肠杆菌和铜绿假单胞菌，以及革兰氏阳性菌枯草芽孢杆菌和金黄色葡萄球菌，以及真菌近平滑念珠菌。肽处理细菌的荧光研究，结合肽对脂质体的影响分析，表明肽发挥了类似于用“经典”人类抗菌肽 LL-37 处理后的膜破坏作用。然而，与 LL-37 不同的是，在存在带负电荷的（细菌模拟）脂质体时，对于 PrP 衍生的肽，没有检测到明显的螺旋诱导。此外，PrP 在人体皮肤的体外和体内创伤以及体外角质形成细胞与 TGF-α的刺激中表现出诱导表达。
PrP 具有抗菌活性的证明，其活性定位于 N 端和肝素结合区，以及在创伤过程中 PrP 表达增加的结果表明，PrP 可能在宿主防御中具有以前未被发现的作用。
