Author(s):
Martins, Ingrid Bernardes Santana [UNESP] ; Viegas, Taisa Giordano [UNESP] ; dos Santos Alvares, Dayane [UNESP] ; de Souza, Bibiana Monson [UNESP] ; Palma, Mário Sérgio [UNESP] ; Ruggiero Neto, João [UNESP] ; de Araujo, Alexandre Suman [UNESP]
Date: 2021
Persistent ID: http://hdl.handle.net/11449/207666
Origin: Oasisbr
Subject(s): Antimicrobial peptides; Conformational analysis; Lytic activity; Molecular dynamics simulation; pH sensitive peptide; Antimicrobial peptides; Antimicrobial peptides; Conformational analysis; Conformational analysis; Lytic activity; Lytic activity; Molecular dynamics simulation; Molecular dynamics simulation; pH sensitive peptide; pH sensitive peptide
Description
Made available in DSpace on 2021-06-25T10:59:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01
Antimicrobial peptides (AMPs) are part of the innate immune system of many species. AMPs are short sequences rich in charged and non-polar residues. They act on the lipid phase of the plasma membrane without requiring membrane receptors. Polybia-MP1 (MP1), extracted from a native wasp, is a broad-spectrum bactericide, an inhibitor of cancer cell proliferation being non-hemolytic and non-cytotoxic. MP1 mechanism of action and its adsorption mode is not yet completely known. Its adsorption to lipid bilayer and lytic activity is most likely dependent on the ionization state of its two acidic and three basic residues and consequently on the bulk pH. Here we investigated the effect of bulk acidic (pH 5.5) and neutral pH (7.4) solution on the adsorption, insertion, and lytic activity of MP1 and its analog H-MP1 to anionic (7POPC:3POPG) model membrane. H-MP1 is a synthetic analog of MP1 with lysines replaced by histidines. Bulk pH changes could modulate this peptide efficiency. The combination of different experimental techniques and molecular dynamics (MD) simulations showed that the adsorption, insertion, and lytic activity of H-MP1 are highly sensitive to bulk pH in opposition to MP1. The atomistic details, provided by MD simulations, showed peptides contact their N-termini to the bilayer before the insertion and then lay parallel to the bilayer. Their hydrophobic faces inserted into the acyl chain phase disturb the lipid-packing.
Department of Physics IBILCE UNESP-São Paulo State University, Cristóvão Colombo, 2265-Jardim Nazareth
Department of Basic and Applied Biology Institute of Biosciences UNESP-São Paulo State University
Department of Physics IBILCE UNESP-São Paulo State University, Cristóvão Colombo, 2265-Jardim Nazareth
Department of Basic and Applied Biology Institute of Biosciences UNESP-São Paulo State University
