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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).


This family belongs to the: Cecropin Superfamily.

References associated with 1.C.52 family:

Bessin, Y., N. Saint, L. Marri, D. Marchini, and G. Molle. (2004). Antibacterial activity and pore-forming properties of ceratotoxins: a mechanism of action based on the barrel stave model. Biochim. Biophys. Acta 1667: 148-156. 15581850
Charpentier, S., M. Amiche, J. Mester, V. Vouille, J.P. Le Caer, P. Nicolas. and A. Delfour. (1998). Structure, synthesis, and molecular cloning of dermaseptins B, a family of skin peptide antibiotics. J. Biol. Chem. 273: 14690-14697. 9614066
Fernandez DI., Gehman JD. and Separovic F. (2009). Membrane interactions of antimicrobial peptides from Australian frogs. Biochim Biophys Acta. 1788(8):1630-8. 19013126
Gusmão, K.A., D.M. Dos Santos, V.M. Santos, M.E. Cortés, P.V. Reis, V.L. Santos, D. Piló-Veloso, R.M. Verly, M.E. de Lima, and J.M. Resende. (2017). Ocellatin peptides from the skin secretion of the South American frog Leptodactylus labyrinthicus (Leptodactylidae): characterization, antimicrobial activities and membrane interactions. J Venom Anim Toxins Incl Trop Dis 23: 4. 28115922
Hu, K., Y. Jiang, Y. Xie, H. Liu, R. Liu, Z. Zhao, R. Lai, and L. Yang. (2015). Small-Anion Selective Transmembrane "Holes" Induced by an Antimicrobial Peptide Too Short to Span Membranes. J Phys Chem B 119: 8553-8560. 26126210
Mahalka, A.K. and P.K. Kinnunen. (2009). Binding of amphipathic α-helical antimicrobial peptides to lipid membranes: lessons from temporins B and L. Biochim. Biophys. Acta. 1788: 1600-1609. 19394305
Mechler, A., S. Praporski, K. Atmuri, M. Boland, F. Separovic, and L.L. Martin. (2007). Specific and selective peptide-membrane interactions revealed using quartz crystal microbalance. Biophys. J. 93: 3907-3916. 17704161
Moll, G.N., S. Brul, W.N. Konings, and A.J. Driessen. (2000). Comparison of the membrane interaction and permeabilization by the designed peptide Ac-MB21-NH2 and truncated dermaseptin S3. Biochemistry 39: 11907-11912. 11009603
Nicolas P. and El Amri C. (2009). The dermaseptin superfamily: a gene-based combinatorial library of antimicrobial peptides. Biochim Biophys Acta. 1788(8):1537-50. 18929530
Nicolas, P. and A. Mor. (1995). Peptides as weapons against microorganisms in the chemical defense system of vertebrates. Annu. Rev. Microbiol. 49: 277-304. 8561461
Rinaldi, A.C. (2002). Antimicrobial peptides from amphibian skin: an expanding scenario. Curr. Opin. Chem. Biol. 6: 799-804. 12470734
Rinaldi, A.C., M.L. Mangoni, A. Rufo, C. Luzi, D. Barra, H. Zhao, P.K.J. Kinnunen, A. Bozzi, A. Di Giulio, and M. Simmaco. (2002). Temporin L: antimicrobial, haemolytic and cytotoxic activities, and effects on membrane permeabilization in lipid vesicles. Biochem. J. 368: 91-100. 12133008
Sherman, P.J., R.J. Jackway, J.D. Gehman, S. Praporski, G.A. McCubbin, A. Mechler, L.L. Martin, F. Separovic, and J.H. Bowie. (2009). Solution structure and membrane interactions of the antimicrobial peptide fallaxidin 4.1a: an NMR and QCM study. Biochemistry 48: 11892-11901. 19894755
Tamang, D.G. and M.H. Saier, Jr. (2006). The cecropin superfamily of toxic peptides. J. Mol. Microbiol. Biotechnol. 11: 94-103. 16825792
Zhao, H., A.C. Rinaldi, A. Di Giulio, M. Simmaco, and P.K.J. Kinnunen. (2002). Interactions of the antimicrobial peptides temporins with model biomembranes. Comparison of temporins B and L. Biochemistry 41: 4425-4436. 11914090