| 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)
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This family belongs to the Cecropin Superfamily.
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| References: |
Ammar, B., A. Périanin, A. Mor, G. Sarfati, M. Tissot, P. Nicolas, J.P. Giroud, and M. Roch-Arveiller. (1998). Dermaseptin, a peptide antibiotic, stimulates microbicidal activities of polymorphonuclear leukocytes. Biochem. Biophys. Res. Commun. 247: 870-875.
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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.
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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.
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Fernandez DI., Gehman JD. and Separovic F. (2009). Membrane interactions of antimicrobial peptides from Australian frogs. Biochim Biophys Acta. 1788(8):1630-8.
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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.
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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.
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Liu, Y., X. Shao, T. Wang, X. Wang, N. Li, Y. Zhao, W. Xia, and L. Sun. (2021). [Structure prediction and biological activity analysis of dybowskin-1ST antimicrobial peptide in Rana dybowskii]. Sheng Wu Gong Cheng Xue Bao 37: 2890-2902.
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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.
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Mayer, S.F., J. Ducrey, J. Dupasquier, L. Haeni, B. Rothen-Rutishauser, J. Yang, A. Fennouri, and M. Mayer. (2019). Targeting specific membranes with an azide derivative of the pore-forming peptide ceratotoxin A. Biochim. Biophys. Acta. Biomembr 1861: 183023.
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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.
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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.
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Mor, A. and P. Nicolas. (1994). Isolation and structure of novel defensive peptides from frog skin. Eur J Biochem 219: 145-154.
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Mor, A. and P. Nicolas. (1994). The NH2-terminal α-helical domain 1-18 of dermaseptin is responsible for antimicrobial activity. J. Biol. Chem. 269: 1934-1939.
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Mor, A., V.H. Nguyen, A. Delfour, D. Migliore-Samour, and P. Nicolas. (1991). Isolation, amino acid sequence, and synthesis of dermaseptin, a novel antimicrobial peptide of amphibian skin. Biochemistry 30: 8824-8830.
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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.
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Nicolas, P. and A. Mor. (1995). Peptides as weapons against microorganisms in the chemical defense system of vertebrates. Annu. Rev. Microbiol. 49: 277-304.
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Rinaldi, A.C. (2002). Antimicrobial peptides from amphibian skin: an expanding scenario. Curr. Opin. Chem. Biol. 6: 799-804.
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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.
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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.
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Tamang, D.G. and M.H. Saier, Jr. (2006). The cecropin superfamily of toxic peptides. J. Mol. Microbiol. Biotechnol. 11: 94-103.
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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.
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| Examples: |
| TC# | Name | Organismal Type | Example |
| 1.C.52.1.1 | Dermaseptin B1 precursor | Amphibians | Dermaseptin B1 of Phyllomedusa bicolor |
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| 1.C.52.1.10 | PBN1 precursor | Amphibians | PBN1 precursor of Phyllomedusa bicolor |
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| 1.C.52.1.11 | Preprofallaxidin-6 (green tree frog) (71% identical to 1.C.52.1.9). The NMR structure of the mature peptide (Fallaxidin 4.1a) reveals a helical structure in detergent solultions. Pore formation is established (Sherman et al. 2009). | Amphibians | Fallaxidin of Litoria fallax (B5LUQ8) |
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| 1.C.52.1.12 | Phylloseptin-7 (orange legged leaf frog) (81% identical to 1.C.52.1.10).
| Amphibians | Phylloseptin of Phyllomedusa hypochondrialis (P84572) |
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| 1.C.52.1.13 | Raniseptin-1 (55% identical to 1.C.52.1.1).
| Amphibians | Raniseptin-1 of Hypsiboas raniceps (P86037) |
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| 1.C.52.1.14 | Kininogen-1 (71% identical to 1.C.52.1.10).
| Amphibians | Kininogen-1 of Phyllomedusa sauvagei (Q800F1). |
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| 1.C.52.1.15 | Vespakinin-M precursor (also homologous to Melittin)
| Wasps | Vespakinin of Vespa magnifica (Q0PQX8) |
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| 1.C.52.1.16 | Brevienin-1E of 71 aas | Amphibians (frog) | Brevenin-iE of Pelophylex esulentus |
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| 1.C.52.1.17 | Ranakinin-N of 58 aas | Amphibians (frog) | Ranakinin-N of Hylarana nigrovittata |
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| 1.C.52.1.18 | Prepromelittin amphibian defense peptide | Amphibians | Prepromelittin of Rana andersonii (E3SZK1) |
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| 1.C.52.1.19 | Rufosusi-spotted torrent frog Amolopin-3a anti-microbial peptide | Amphibians | Amolopin-3a of Amolops loloensis (A6XFB5) |
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| 1.C.52.1.2 | Brevinin 2EF precursor | Amphibians | Brevinin-2EF of Rana esculenta |
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| 1.C.52.1.20 | Demaseptin-1 | Amphibians | Dermaseptin-1 of Phyllomedusa hypochondrialis (P84596) |
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| 1.C.52.1.21 | Brevinin-2HS of 70 aas and 2 TMSs. | Animals | Brevinin-2HS of Odorrana schmackeri (Schmacker's frog) (Rana schmackeri) |
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| 1.C.52.1.22 | Rhacophorin-2 of 72 aas and 2 TMSs. | Animals | Rhacophori-2 of Rhacophorus feae (Thao whipping frog) |
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| 1.C.52.1.23 | Hainanensin-1 of 67 aas and 2 TMSs | Animals | Hainanensin-1 of Odorrana hainanensis (Odor frog) (Rana hainanensis) |
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| 1.C.52.1.24 | Amurin-1 of 70 aas and 2 TMSs | Animals | Amurin-1 of Rana amurensis (Korean brown frog) |
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| 1.C.52.1.25 | Viridimin-1 of 66 aas and 2 TM | Animals | Viridimin-1 of Amolops viridimaculatus (Dahaoping sucker frog) |
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| 1.C.52.1.26 | Amolopin-1a of 70 aas | Animals | Amolopin-1a of Amolops loloensis (rufous-spotted torrent frog) |
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| 1.C.52.1.27 | Andersonin of 72 aas | Animals | Andersonin of Odorrana andersonii (golden crossband frog) |
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| 1.C.52.1.28 | Lividin-1 of 68 aas | Animals | Lividin-1 of Odorrana livida (green cascade frog) |
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| 1.C.52.1.29 | Kunyuenin of 62 aas | Animals | Kunyuenin of Rana kunyuensis |
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| 1.C.52.1.3 | Gaegurin-4 precursor | Amphibians | Gaegurin-4 of Rana rugosa |
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| 1.C.52.1.30 | Japonicin-1Ja of 61 aas | Animals | Japonicin-1Ja of Rana japonica (Japanese reddish frog) |
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| 1.C.52.1.31 | Limnonectin-1Fa of 62 aas | Animals | Limnonectin-1Fa of Limnonectes fujianensis (Fujian large-headed frog) |
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| 1.C.52.1.32 | Jingdongin-1 of 63 aas | Animals | Jingdongin-1 of Amolop jingdongensis (Chinese torrent frog)
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| 1.C.52.1.33 | Frenatin-3 of 68 aas | Animals | Frenatin-2 of Litoria infrafrenata (Giant tree frog) (White-lipped tree frog) |
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| 1.C.52.1.34 | Antimicrobial peptide odorranain B4 of 63 aas. A 15 aa disulfide bonded peptide, ORB-1 (LKGCWTKSIPPKPCF), too short to pass through a membrane, forms anion selective channels (Hu et al. 2015).
| Animals | odorranain B4 of Odorrana grahami (Yunnanfu frog) (Rana grahami) |
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| 1.C.52.1.35 | Pore-forming Ocellatin-PT1 of 66 aas (Gusmão et al. 2017). | | Ocellatin-PT1 of Leptodactylus pustulatus (Ceara white-lipped frog) |
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| 1.C.52.1.36 | Dybowskin-1ST antimicrobial peptide of 59 aas. It has an N-terminal TMS with a largely hydrophilic central region with an α-helical structure. It promotes wound healing and effectively inhibits the growth of Escherichia coli and Staphylococcus aureus (Liu et al. 2021).
| | antimicrobial peptide of Rana dybowskii (Dybovsky's frog) (Korean brown frog) |
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| 1.C.52.1.37 | Dermaseptin S1, Drs1, of 79 aas and 1 or 2 TMSs with the first N-terminal TMS being more hydrophobic than the second C-terminal TMS. The central region is very hydrophilic. It is 90% identical to Dermaseptin B1 (TC# 1.C.52.1.1) at the sequence level. It shows antimicrobial activity with potent activity against Gram-positive and Gram-negative bacteria, fungi and protozoa (Mor et al. 1991, Mor and Nicolas 1994). It also stimulates the microbicidal activity of polymorphonuclear leukocytes (Ammar et al. 1998) and may act by disturbing membrane functions with its amphipathic structure (Mor and Nicolas 1994). | | Dermaseptin S1 of Phyllomedusa sauvagei (Sauvage's leaf frog)
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| 1.C.52.1.4 | Esculentin-1b precursor | Amphibians | Esculentin-1b of Rana esculenta |
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| 1.C.52.1.5 | Temporin G precursor | Amphibians | Temporin G precursor of Rana temporaria |
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| 1.C.52.1.6 | Temporin B precursor | Amphibians | Temporin B precursor of Rana temporaria |
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| 1.C.52.1.7 | Ranatuerin-2P precursor | Amphibians | Ranatuerin-2P precursor of Rana pipiens |
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| 1.C.52.1.8 | Tryptophyllin-1 precursor | Amphibians | Tryptophyllin-1 precursor of Pachymedusa dacnicolor |
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| 1.C.52.1.9 | Caerin 1.1.5 precursor; similar to maculatin 1.1 of Litoria genimaculata (1.C.76.1.1) (Fernandez et al., 2008; Mechler et al., 2007).
| Amphibians | Caerin 1.1.5 precursor of Litoria caerulea |
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| Examples: |
| TC# | Name | Organismal Type | Example |
| 1.C.52.2.1 | Ceratotoxin A, CtxA, of 72 aas and 2 TMSs. It forms one of the largest pores among the group of ceratotoxins (Mayer et al. 2019). | Insects | CtxA of Ceratitis capitata (medfly) (P36190) |
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| 1.C.52.2.2 | Ceratotoxin-B of 29 aas, corresponding to the C-terminal region of Ceratotoxin A. | | Ceratotoxin-B of Ceratitis capitata (Mediterranean fruit fly) |
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| 1.C.52.2.3 | Ceratotoxin 2 of 40 aas and 1 N-terminal TMS. | | Ceretotoxin 2 of Ceratitis rosa (Natal fruit fly) |
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