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)
Dermaseptin B1 precursor
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).
Fallaxidin of Litoria fallax (B5LUQ8)
Phylloseptin of Phyllomedusa hypochondrialis (P84572)
Raniseptin-1 of Hypsiboas raniceps (P86037)
Kininogen-1 of Phyllomedusa sauvagei (Q800F1).
Vespakinin of Vespa magnifica (Q0PQX8)
Brevienin-1E of 71 aas
Brevenin-iE of Pelophylex esulentus
Ranakinin-N of 58 aas
Ranakinin-N of Hylarana nigrovittata
Prepromelittin amphibian defense peptide
Prepromelittin of Rana andersonii (E3SZK1)
Rufosusi-spotted torrent frog Amolopin-3a anti-microbial peptide
Amolopin-3a of Amolops loloensis (A6XFB5)
Dermaseptin-1 of Phyllomedusa hypochondrialis (P84596)
Brevinin-2HS of 70 aas and 2 TMSs.
Brevinin-2HS of Odorrana schmackeri (Schmacker's frog) (Rana schmackeri)
Rhacophorin-2 of 72 aas and 2 TMSs.
Rhacophori-2 of Rhacophorus feae (Thao whipping frog)
Hainanensin-1 of 67 aas and 2 TMSs
Hainanensin-1 of Odorrana hainanensis (Odor frog) (Rana hainanensis)
Amurin-1 of 70 aas and 2 TMSs
Amurin-1 of Rana amurensis (Korean brown frog)
Viridimin-1 of 66 aas and 2 TM
Viridimin-1 of Amolops viridimaculatus (Dahaoping sucker frog)
Amolopin-1a of 70 aas
Amolopin-1a of Amolops loloensis (rufous-spotted torrent frog)
Andersonin of 72 aas
Andersonin of Odorrana andersonii (golden crossband frog)
Lividin-1 of 68 aas
Lividin-1 of Odorrana livida (green cascade frog)
Kunyuenin of 62 aas
Kunyuenin of Rana kunyuensis
Japonicin-1Ja of 61 aas
Japonicin-1Ja of Rana japonica (Japanese reddish frog)
Limnonectin-1Fa of 62 aas
Limnonectin-1Fa of Limnonectes fujianensis (Fujian large-headed frog)
Jingdongin-1 of 63 aas
Jingdongin-1 of Amolop jingdongensis (Chinese torrent frog)
Frenatin-3 of 68 aas
Frenatin-2 of Litoria infrafrenata (Giant tree frog) (White-lipped tree frog)
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).
odorranain B4 of Odorrana grahami (Yunnanfu frog) (Rana grahami)
Pore-forming Ocellatin-PT1 of 66 aas (Gusmão et al. 2017).
Ocellatin-PT1 of Leptodactylus pustulatus (Ceara white-lipped frog)
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)
Caerin 1.1.5 precursor of Litoria caerulea
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).
CtxA of Ceratitis capitata (medfly) (P36190)
Ceratotoxin-B of 29 aas, corresponding to the C-terminal region of Ceratotoxin A.
Ceratotoxin-B of Ceratitis capitata (Mediterranean fruit fly)
Ceratotoxin 2 of 40 aas and 1 N-terminal TMS.
Ceretotoxin 2 of Ceratitis rosa (Natal fruit fly)