Dodecapeptide Cathelicidins of Cetartiodactyla: Structure, Mechanism of Antimicrobial Action, and Synergistic Interaction With Other Cathelicidinsстатья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 23 сентября 2021 г.
Аннотация:In this study, dodecapeptide cathelicidins were shown to be widespread antimicrobial
peptides among the Cetruminantia clade. In particular, we investigated the
dodecapeptide from the domestic goat Capra hircus, designated as ChDode and its
unique ortholog from the sperm whale Physeter catodon (PcDode). ChDode contains
two cysteine residues, while PcDode consists of two dodecapeptide building blocks
and contains four cysteine residues. The recombinant analogs of the peptides were
obtained by heterologous expression in Escherichia coli cells. The structures of the
peptides were studied by circular dichroism (CD), FTIR, and NMR spectroscopy. It
was demonstrated that PcDode adopts a b-hairpin structure in water and resembles
b-hairpin antimicrobial peptides, while ChDode forms a b-structural antiparallel covalent
dimer, stabilized by two intermonomer disulfide bonds. Both peptides reveal a significant right-handed twist about 200 degrees per 8 residues. In DPC micelles ChDode forms flat beta-structural tetramers by antiparallel non-covalent association of the dimers. Thetetramers incorporate into the micelles in transmembrane orientation. Incorporation into the micelles and dimerization significantly diminished the amplitude of backbone motions of ChDode at the picosecond-nanosecond timescale. When interacting with negatively charged membranes containing phosphatidylethanolamine (PE) and
phosphatidylglycerol (PG), the ChDode peptide adopted similar oligomeric structure and
was capable to form ion-conducting pores without membrane lysis. Despite modest
antibacterial activity of ChDode, a considerable synergistic effect of this peptide in combination with another goat cathelicidin – the alpha-helical peptide ChMAP-28 was observed. This effect is based on an increase in permeability of bacterial membranes. In turn, this mechanism can lead to an increase in the efficiency of the combined action of the synergistic pair ChMAP-28 with the Pro-rich peptide mini-ChBac7.5Na targeting
the bacterial ribosome.