Plasticins: membrane-damaging peptides with ‘chameleon-like’ properties

Abstract

Plasticins belong to the dermaseptin superfamily of gene-encoded, membrane-active host defense peptides produced by the skin of hylid frogs. The plasticins, which are rich in Gly and Leu residues arranged in regular 5-mer motifs GXXXG (where X is any amino acid residue), have very similar amino acid sequences, hydrophobicities, and amphipathicities but differ markedly in their net charge, conformational plasticity, and activity spectra. The intrinsic flexibility and structural malleability of plasticins modulate their ability to bind to and disrupt the membranes of prokaryotic and eukaryotic cells, and/or to reach intracellular targets, therefore triggering functional versatility. This family of closely related but functionally divergent peptides constitutes a good model to address the relationships between structural polymorphism, membrane-interacting properties, and the biological activity of antimicrobial, cell-penetrating, and viral fusion peptides. Plasticins could thus serve as templates to design potent multifunctional drugs that could act simultaneously against bacterial pathogens and viruses.

Structural diversity and species distribution of host-defense peptides in frog skin secretions

“…The Central and South American treefrogs, particularly species in the genera Agalychnis, Hylomantis, Pachymedusa, and Phyllomedusa in the subfamily Phyllomedusinae, have proved to be a rich source of antimicrobial peptides. The diversity in structure and properties of these peptides has been the subject of several detailed reviews [7,12,55] and so this article will present only an overview. As indicated in Table 2, the antimicrobial peptides may be grouped into five major families on the basis of amino acid sequence similarity.…”

“…The plasticins may be divided into two classes on the basis of their cytolytic activities. The strongly cationic peptides that contain multiple lysine residues (plasticin-B1 and -S1) show potent, broad-spectrum antimicrobial activity and will lyse erythrocytes whereas the weakly cationic or neutral plasticins (plasticin-A1, -C1, -C2, and DA1) are hemolytic only [55].…”

Antimicrobial Peptides: New Frontiers in the Therapy of Infections

“…These peptides constitute a rich arsenal of broad-spectrum, cytolytic AMPs characterized by highly variable sequences (Vanhoye et al, 2003). It is estimated that there may be as many as 10 5 different peptides produced by the known 5000 species of anuran amphibians, and more than 400 have been already identified from South American Hylidae or European, Asian or North American Ranidae amphibians (Nicolas & El Amri, 2008). Therefore, the main work still concerns the screening and identification of the most useful factors.…”

“…Basic research on dermaseptins is of relevance because genetic studies on the evolution and diversity of frog skin AMPs may lead to the identification of new peptides with alternative targets. In addition, the discovery of new isoforms with novel structural and biochemical properties may also shed light on the exact roles of various parameters, such as net charge, percent of -helical/ -sheet structure, amphipathy and conformational flexibility, on the ability of antimicrobial peptides to bind to and disrupt bacterial membranes (Nicolas & El Amri, 2008). Dermaseptin antimicrobial activity is currently being characterized and analogs are being developed.…”

“…However, in contrast to the other plasticins, it does not produce lysis of human erythrocytes at concentrations up to 500 M (Conlon et al, 2009). The plasticin peptide family constitutes a good model to address the relationships between structural polymorphism, membrane-interacting property, and biological activity of antimicrobial, cell-penetrating, and viral fusion peptides (El Amri & Nicolas, 2008). Unlike amphipathic helical dermaseptins, plasticins display considerable conformational flexibility and polymorphism that modulate their ability to bind to and disrupt the bilayer membranes of prokaryotic and eukaryotic cells, and/or to reach intracellular targets (Nicolas & El Amri, 2008).…”