Novel antimicrobial anionic cecropins from the spruce budworm feature a poly-L-aspartic acid C-terminus

Autor: Marianne Potvin, Roger C. Levesque, Halim Maaroufi, Michel Cusson
Rok vydání: 2021
Předmět:
Protein Conformation
alpha-Helical
animal structures
Static Electricity
Peptide
Antineoplastic Agents
Apoptosis
Molecular Dynamics Simulation
Moths
Biochemistry
Evolution
Molecular
03 medical and health sciences
Structural Biology
Aspartic acid
Escherichia coli
Animals
Humans
Protein Interaction Domains and Motifs
Amino Acid Sequence
Molecular Biology
Phylogeny
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
Binding Sites
biology
C-terminus
fungi
030302 biochemistry & molecular biology
Cecropins
Cationic polymerization
Antimicrobial
biology.organism_classification
3. Good health
Anti-Bacterial Agents
Cecropin
chemistry
Proto-Oncogene Proteins c-bcl-2
Insect Proteins
Antibacterial activity
Peptides
Hydrophobic and Hydrophilic Interactions
Bacteria
Protein Binding
Zdroj: ProteinsREFERENCES. 89(9)
ISSN: 1097-0134
Popis: Cecropins form a family of amphipathic α-helical cationic peptides with broad-spectrum antibacterial properties and potent anticancer activity. The emergence of bacteria and cancer cells showing resistance to cationic antimicrobial peptides (CAMPs) has fostered a search for new, more selective and more effective alternatives to CAMPs. With this goal in mind, we looked for cecropin homologs in the genome and transcriptome of the spruce budworm, Choristoneura fumiferana. Not only did we find paralogs of the conventional cationic cecropins (Cfcec+ ), our screening also led to the identification of previously uncharacterized anionic cecropins (Cfcec- ), featuring a poly-l-aspartic acid C-terminus. Comparative peptide analysis indicated that the C-terminal helix of Cfcec- is amphipathic, unlike that of Cfcec+ , which is hydrophobic. Interestingly, molecular dynamics simulations pointed to the lower conformational flexibility of Cfcec- peptides, relative to that of Cfcec+ . Phylogenetic analysis suggests that the evolution of distinct Cfcec+ and Cfcec- peptides may have resulted from an ancient duplication event within the Lepidoptera. Finally, we found that both anionic and cationic cecropins contain a BH3-like motif (G-[KQR]-[HKQNR]-[IV]-[KQR]) that could interact with Bcl-2, a protein involved in apoptosis; this observation is congruent with previous reports indicating that cecropins induce apoptosis. Altogether, our observations suggest that cecropins may provide templates for the development of new anticancer drugs. We also estimated the antibacterial activity of Cfcec-2 and a ∆Cfce-2 peptide as AMPs by testing directly their ability in inhibiting bacterial growth in a disk diffusion assay and their potential for development of novel therapeutics.
Databáze: OpenAIRE
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