Abstract
Endogenous antimicrobial peptides (AMPs) are among the earliest molecular factors in the evolution of animal innate immunity. In this study, novel AMPs named nicomicins were identified in the small marine polychaeta Nicomache minor in the Maldanidae family. Full-length mRNA sequences encoded 239-residue prepropeptides consisting of a putative signal sequence region, the BRICHOS domain within an acidic proregion, and 33-residue mature cationic peptides. Nicomicin-1 was expressed in the bacterial system, and its spatial structure was analyzed by circular dichroism and nuclear magnetic resonance spectroscopy. Nicomicins are unique among polychaeta AMPs scaffolds, combining an amphipathic N-terminal α-helix and C-terminal extended part with a six-residue loop stabilized by a disulfide bridge. This structural arrangement resembles the Rana-box motif observed in the α-helical host-defense peptides isolated from frog skin. Nicomicin-1 exhibited strong in vitro antimicrobial activity against Gram-positive bacteria at submicromolar concentrations. The main mechanism of nicomicin-1 action is based on membrane damage but not on the inhibition of bacterial translation. The peptide possessed cytotoxicity against cancer and normal adherent cells as well as toward human erythrocytes.
Highlights
Endogenous antimicrobial peptides (AMPs), known as host-defense peptides (HDPs), are among the most ancient molecular components of the innate immunity system that contribute to the first line of defense against pathogens of most life forms [1]
There are a number of methods for searching for novel AMPs: direct peptide isolation from tissues and cells, whole genome and/or transcriptome sequencing followed by bioinformatic analysis, cloning of cDNA amplified by primers targeting for conserved regions
This domain has been reported for precursors of five AMPs: arenicin-1 and -2 [4], arenicin-3 known as NZ17000 [12], alvinellacin [8], and capitellacin [8]
Summary
Endogenous antimicrobial peptides (AMPs), known as host-defense peptides (HDPs), are among the most ancient molecular components of the innate immunity system that contribute to the first line of defense against pathogens of most life forms [1]. Polychaeta is a largely unexplored class of invertebrates in the context of discovery of new AMPs. The large majority of polychaeta species are marine animals that inhabit all places, from the Arctic to the Antarctic, and from the littoral zone to the deepest depths of the oceans. The large majority of polychaeta species are marine animals that inhabit all places, from the Arctic to the Antarctic, and from the littoral zone to the deepest depths of the oceans They are considered the most primitive annelids, based on morphology, physiology, and development [3]
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