The effect of acidic pH on the adsorption and lytic activity of the peptides Polybia-MP1 and its histidine-containing analog in anionic lipid membrane: a biophysical study by molecular dynamics and spectroscopy

Author(s)

Santana Martins, Ingrid Bernardes ^[1] ; Viegas, Taisa Giordano ^[1] ; Alvares, Dayane dos Santos ^[1] ; de Souza, Bibiana Monson ^[2] ; Palma, Mario Sergio ^[2] ; Neto, Joao Ruggiero ^[1] ; de Araujo, Alexandre Suman ^[1]

Affiliation

^[1] UNESP Sao Paulo State Univ, Dept Phys, IBILCE, 2265 Jardim Nazareth, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

^[2] UNESP Sao Paulo State Univ, Inst Biosci, Dept Basic & Appl Biol, Rio Claro, SP - Brazil

• Document type: Journal article
• Source: Amino Acids; v. 53, n. 5, p. 753-767, MAY 2021.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 15/25619-9 - Effect of aminophospholipids and of the pH on the interfacial activity of the anticancer peptide Polybia-MP1 and analogs in model membranes
• Grantee: João Ruggiero Neto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/16212-5 - Natural proteopeptides from the Brazilian fauna, flora and microbiota as potential models for the rational development of new drugs of therapeutic use: isolation, structure elucidation, chemical synthesis and functional activity assays
• Grantee: Mario Sergio Palma
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 15/25620-7 - Interaction membrane/peptide: mechanical and electrostatic properties in system with lipid domains
• Grantee: Dayane dos Santos Alvares
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 10/18169-3 - Investigations of physical chemistry processes related with the binding of environmental relevant heavy metal ions by calix[4]arenes using molecular dynamics simulations
• Grantee: Alexandre Suman de Araujo
• Support Opportunities: Regular Research Grants