1.C.17 The Cecropin (Cecropin) Family
Many organisms synthesize proteins (or peptides) which are degraded to relatively small hydrophobic or amphipathic, bioactive peptides. These peptides exhibit antibiotic, fungicidal, virucidal, hemolytic and/or tumoricidal activities by interacting with membranes and forming transmembrane channels that allow the free flow of electrolytes, metabolites and water across the phospholipid bilayers. Most of these peptides appear to function in biological warfare. There are many designations given to these bioactive peptides. They include the magainins, cecropins, melittins, defensins, bacteriocidins, etc. The proteins in each family within this functional superfamily are homologous, but they exhibit little or no significant sequence similarity with members of the other families. Thus, each family may have evolved independently. However, certain common structural features observed between members of distinct families suggest that at least some of these families share a common ancestry. The inhibition of steady-state transmembrane current produced by the antimicrobial peptide, cecropin A, was attributed to both the dipole potential drop and membrane lipid disordering in the presence of pepper alkaloids (Efimova et al. 2020).
Cecropins are produced by insects, particularly under conditions of
infection. Cecropins A, B and D are close homologues consisting of
35-39 residues. They are found in the pupae of the cecropin moth, but
related homologues named lepodopteran, bactericidin, moricin and
sarcotoxin are produced by other insects. Several families of eukaryotic channel-forming amphipathic peptide, each
from a different group of organisms, are recognized. Non-insect derived
cecropin-like peptides are members of the Cecropin superfamily.
Peptides, indolicidin, aurein 1.2, magainin II, cecropin A and LL-37 all
cause a general acceleration of essential lipid transport processes
without altering the overall structure of the lipid membranes or
creating organized pore-like structures (Nielsen et al. 2020).
Rapid scrambling of the lipid composition associated with enhanced
lipid transport may trigger lethal signaling processes and enhance ion
The generalized transport reaction catalyzed by channel-forming amphipathic peptides is:
small solutes, electrolytes and water (in) small solutes, electrolytes and water (out).
This family belongs to the Cecropin Superfamily.
|Bechinger, B. (1997). Structure and functions of channel-forming peptides: magainins, cecropins, melittin and alamethicin. J. Membr. Biol. 156: 197-211.|
|Bechinger, B., M. Zasloff and S.J. Opella (1993). Structure and orientation of the antibiotic peptide magainin in membrane by solid-state nuclear magnetic resonance spectroscopy. Prot. Sci. 2: 2077-2084.|
|Efimova, S.S., A.A. Zakharova, and O.S. Ostroumova. (2020). Alkaloids Modulate the Functioning of Ion Channels Produced by Antimicrobial Agents via an Influence on the Lipid Host. Front Cell Dev Biol 8: 537.|
|Efimova, S.S., L.V. Schagina, and O.S. Ostroumova. (2014). Channel-forming activity of cecropins in lipid bilayers: effect of agents modifying the membrane dipole potential. Langmuir 30: 7884-7892.|
|Ganz, T., J.R. Rayner, E.V. Valore, A. Tumolo, K. Talmadge and F. Fuller (1989). The structure of the rabbit macrophage defensin genes and their organ-specific expression. J. Immunol. 143: 1358-1365.|
|Gudmundsson, G.H., D.A. Lidholm, B. Asling, R.B. Gan and H.G. Boman (1991). The cecropin locuscloning and expression of a gene cluster encoding 3 antibacterial peptides in Hyalophora cecropia. J. Biol. Chem. 266: 11510-11517.|
|Hill, C.P., J. Yee, M.E. Selsted and D. Eisenberg (1991). Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization. Science 251: 1481-1485.|
|Lee, I.H., C. Zhao, Y. Cho, S.S. Harwig, E.L. Cooper, and R.I. Lehrer. (1997). Clavanins, α-helical antimicrobial peptides from tunicate hemocytes. FEBS Lett. 400: 158-162. |
|Matsuzaki, K. (1998). Magainins as paradigm for the mode of action of pore forming polypeptides. Biochim. Biophys. Acta 1376: 391-400.|
|Nagaoka, I., A. Someya, K. Iwabuchi and T. Yamashita (1991). Characterization of cDNA clones encoding guinea pig neutrophil cationic peptides. FEBS Lett. 280: 287-291.|
|Nielsen, J.E., V.A. Bjørnestad, V. Pipich, H. Jenssen, and R. Lund. (2020). Beyond structural models for the mode of action: How natural antimicrobial peptides affect lipid transport. J Colloid Interface Sci 582: 793-802. [Epub: Ahead of Print]|
|Pardi, A., X.L. Zhang, M.E. Selsted, J.J. Skalicky and P.F. Yip (1992). NMR studies of defensin antimicrobial peptides. 2. Three-dimensional structures of rabbit NP-2 and human HNP-1. Biochemistry 31: 11357-11364.|
|Tamang, D.G. and M.H. Saier, Jr. (2006). The cecropin superfamily of toxic peptides. J. Mol. Microbiol. Biotechnol. 11: 94-103. |
|Taylor, S.W., A.G. Craig, W.H. Fischer, M. Park, and R.I. Lehrer. (2000). Styelin D, an extensively modified antimicrobial peptide from ascidian hemocytes. J. Biol. Chem. 275: 38417-38426. |
|Terwilliger, T.C. and D. Eisenberg (1982). The structure of melittin. II. Interpretation of the structure. J. Biol. Chem. 257: 6016-6022.|
|Vlasak, R., C. Unger-Ullmann, G. Kreil and A.M. Frischauf (1983). Nucleotide sequence of cloned cDNA coding for honeybee prepromelittin. Eur. J. Biochem. 135: 123-126.|
|Zhang, X.L., M.E. Selsted and A. Pardi (1992). NMR studies of defensin antimicrobial peptides. 1. Resonance assignment and secondary structure determination of rabbit NP-2 and human HNP-1. Biochemistry 31: 11348-11356.|
|Zhao, C., L. Liaw, I.H. Lee, and R.I. Lehrer. (1997). cDNA cloning of three cecropin-like antimicrobial peptides (Styelins) from the tunicate, Styela clava. FEBS Lett. 412: 144-148. |
Cecropin A, B and C precursor. Cecropin A and B form pores, but cecropin P1 doesn't. Insertion and activity are dependent on the lipids present. Can be cation- or anion-selective, or non-selective. The negative pole of the dipole is probably inserted into the membrane first (Efimova et al. 2014).
Cecropin A, B and C precursor of Hyalophora cecropia
|1.C.17.1.2||Hyphancin III E precursor ||Insects ||Hyphancin III E precursor of Hyphantria cunea|
|1.C.17.1.3||Moricin precursor ||Insects ||Moricin precursor of Bombyx mori|
|1.C.17.1.4||Bactericidin B-5P precursor ||Insects ||Bactericidin B-5P precursor of Manduca sexta|
|1.C.17.1.5||Sarcotoxin IA precursor ||Insects ||Sarcotoxin IA precursor of Sarcophaga peregrina|
|1.C.17.2.1||Styelin D precursor (81 aas) (Taylor et al., 2000)||Tunicate (Seasquirt)||Styelin D of Styela clava (O18495)|
|1.C.17.2.2||The Bradykinin-potentiating peptide homologue (BPPH) with antimicrobial activity (80aas)|
BPPH of Hadrurus gertschi (P0C8L3)
|1.C.17.3.1||Clavanin D precursor (80 aas) (Lee et al., 1997; Zhao et al., 1997)||Tunicate (Seasquirt)||Clavanin D of Styela clava (P80713)|