1.C.52 The Dermaseptin (Dermaseptin) Family

Dermaseptins are antimicrobial peptides, synthesized by frog skin cells with activity against a broad range of organisms (Gram-positive and Gram-negative bacteria, protozoa including Leishmania and Plasmodium species, yeast, and filamentous fungi including species of Aspergillus). There are at least two subgroups of dermaseptins: group B and group S. Functional synergy is observed when different dermaseptin Ss are simultaneously present (>100 x effect). Dermaseptin S3 can be shortened from 30 aas to 16 aas without decreasing activity. These peptides permeabilize biological and artificial membranes. They may form amphipathic α-helical structures, β-structures or mixtures of these, particularly in the presence of anionic lipids. They dissipate the valinomycin-induced membrane potential in liposomes. Dermaseptin S3 inserts more deeply into anionic phospholipid liposomes than those of zwiterionic phospholipids.

Dermaseptins are similiar in sequence to other secreted peptides such as gaegurins, esculentins, brevinins temporins, ranatuerins, tryptophyllins and caerins. They also show sequence similarity with the opioid peptides, dermorphin, dermenkephalin and deltorphins. Finally, they are probably distantly related to ceratotoxins of insects, cecropins of insects (TC #1.C.17), and pleurocidins such as chrysophsin 1 (P83545) from the red sea beam (TC #1.C.62) (Bessin et al., 2004).

Skin secretions of hylid frogs show amazing levels of interspecific and intraspecific diversity and are comprised of a cocktail of genetically-related, but markedly diverse antimicrobial peptides that are grouped into a superfamily, termed the dermaseptins, comprising several families: dermaseptins (sensu stricto), phylloseptins, plasticins, dermatoxins, phylloxins, hyposins, caerins, and aureins. Dermaseptin gene superfamily evolution is characterized by repeated gene duplications and focal hypermutations of the mature peptide coding sequence, followed by positive (diversifying) selection. Nicolas and El Amri, 2008 reviewed molecular mechanisms leading to vast combinatorial peptide libraries.  They also evaluated the structural and functional properties of antimicrobial peptides of the dermaseptin and plasticin families, as well as those of dermaseptin S9, an amyloidogenic peptide with antimicrobial and chemoattractant activities.

Temporins constitute a family of amphipathic alpha-helical antimicrobial peptides (AMP) and contain some of the shortest cytotoxic peptides  comprised of only 10-14 residues. General characteristics of temporins parallel those of other AMP, both in terms of structural features and biophysical properties relating to their interactions with membrane lipids. Selective lipid-binding properties underlie the discrimination between target vs host cells (Mahalka and Kinnunen, 2009). Lipid-binding properties also contribute to the permeabilization of their target cell membranes. The latter functional property of AMP involves highly interdependent acidic phospholipid-induced conformational changes, aggregation, and formation of toxic oligomers in the membrane. These oligomers are subsequently converted to amyloid-type fibers, as demonstrated for temporins B and L, and dermaseptins. The amyloid state represents the generic minimum in the folding/aggregation free energy landscape, and for AMP, its formation most likely serves to detoxify the peptides, in keeping with the current consensus on mature amyloid being inert and non-toxic. This above scenario is supported by sequence analyses of temporins as well as other amphipathic alpha-helical AMP belonging to diverse families. Accordingly, sequence comparison identifies 'conformational switches', domains with equal probabilities for adopting random coil, alpha-helical and beta-sheet structures. These regions aggregate and assemble into amyloid beta-sheets. The lipid-binding properties and structural characterization lend support to the notion that the mechanism of membrane permeabilization by temporins B and L and perhaps of most AMP could be very similar to that of the paradigm amyloid forming cytotoxic peptides responsible for degenerative cell loss in prion, Alzheimer's and Parkinson's diseases, and type 2 diabetes (Mahalka and Kinnunen, 2009).

The reaction presumed to be catalyzed by Dermaseptin family members is:

Ions (in) ions (out)