Cell-Selective Pore Forming Antimicrobial Peptides of the Prodomain of Human Furin: A Conserved Aromatic/Cationic Sequence Mapping, Membrane Disruption, and Atomic-Resolution Structure and Dynamics
journal contributionposted on 2018-11-01, 17:48 authored by Sheetal Sinha, Munesh Kumar Harioudh, Rikeshwer P. Dewangan, Wun Jern Ng, Jimut Kanti Ghosh, Surajit Bhattacharjya
Antimicrobial peptides are promising molecules in uprising consequences of drug-resistant bacteria. The prodomain of furin, a serine protease, expressed in all vertebrates including humans, is known to be important for physiological functions. Here, potent antimicrobial peptides were mapped by extensive analyses of overlapping peptide fragments of the prodomain of human furin. Two peptides, YR26 and YR23, were active against bacterial cells including MRSA-resistant Staphylococcus aureus and Staphylococcus epidermis 51625. Peptides were largely devoid of hemolytic and cytotoxic activity. Bacterial cell killing occurred as a result of the disruption of the permeability barrier of the lipopolysaccharide (LPS)-outer membrane and fragmentation of LPS into small micelles. Furthermore, antibacterial peptides specifically interacted with the negatively charged lipids causing membrane leakage and fusion. The YR26 peptide in sodium dodecyl sulfate micelles demonstrated a long-helix-turn-short-helix structure exhibiting restricted backbone motions. The cell-selective activity of the furin peptides and their unique mode of action on membranes have a significant potential for the development of therapeutics.
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backbone motionsYR 26sodium dodecyl sulfate micellesdrug-resistant bacteriaLPScytotoxic activityserine proteaseCell-Selective Pore Forming Antimicrobial PeptidesMembrane Disruptioncell-selective activityuprising consequencesHuman FurinStaphylococcus epidermis 51625. Peptideslong-helix-turn-short-helix structureAtomic-Resolution StructureMRSA-resistant Staphylococcus aureuspeptide fragmentsmembrane leakageantimicrobial peptidesBacterial cellpermeability barrierDynamics Antimicrobial peptidesfurin peptidesYR 26 peptide