title: Cellular Membrane Composition Requirement by Antimicrobial and Anticancer Peptide GA-K4.
abstract: Naturally occurring antimicrobial peptides important for innate immunity are widely studied for their antimicrobial and anticancer activity. The primary target of these AMPs is believed to be the bacterial cytoplasmic membrane. However, the interaction between cytoplasmic membrane and the antimicrobial peptides remains poorly understood. Therefore to focus on the target membrane composition that is required by AMPs to interact with membranes, we have examined the interaction of the antimicrobial and anticancer active 11-residue GA-K4 (FLKWLFKWAKK) peptide with model and intact cell membranes. Effect on the structural conformational properties of GA-K4 peptide was investigated by means of far-UV CD and fluorescence spectroscopic methods. The different conformation of GA-K4 peptide in large unilamellar vesicles (LUV) bilayer and micelle environment suggest that the curvature has an influence on the secondary structure acquired by the peptide. Furthermore, the leakage experiment result confirmed that GA-K4 induced the leakage of cytoplasmic membrane in Staphylococcus аureus bacterial cells. Fluorescence data revealed the interfacial location of GA-K4 peptide in the model membranes. The blue-shift in emission wavelength by tryptophan residues in fluorescence data indicated the penetration of GA-K4 peptide in micelles and phospholipid bilayers. These results showed that the GA-K4 peptide is a membrane-active peptide and its activity depends on membrane curvature and lipid composition. Although further studies are required to confirm the mechanism of action, the data suggest mechanism of toroidal pore formation for the interaction of GA-K4 peptide with membranes. Our studies will be helpful in better understanding of the membrane requirment of peptides to express their therapeutic effects.
authors.affiliation: Department of Biology, School of Arts & Sciences, National University of Mongolia, Ulaanbaatar 210646, Mongolia.
authors.forename: Tsogbadrakh
authors.initials: T
authors.lastname: Mishig-Ochir
authors.forename: Davaadulam
authors.initials: D
authors.lastname: Gombosuren
authors.forename: Altanchimeg
authors.initials: A
authors.lastname: Jigjid
authors.forename: Badamkhatan
authors.initials: B
authors.lastname: Tuguldur
authors.forename: Galbadrakh
authors.initials: G
authors.lastname: Chuluunbaatar
authors.forename: Enerelt
authors.initials: E
authors.lastname: Urnukhsaikhan
authors.forename: Chinar
authors.initials: C
authors.lastname: Pathak
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea.
authors.forename: Bong-Jin
authors.initials: BJ
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D052160:Benzothiazoles / Q000737:chemistry; D002232:Carbocyanines / Q000737:chemistry; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects; D005456:Fluorescent Dyes / Q000737:chemistry; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry; D008244:Lysophosphatidylcholines / Q000737:chemistry; D008823:Micelles; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D013211:Staphylococcus aureus / Q000737:chemistry / Q000187:drug effects*; D053835:Unilamellar Liposomes / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D052160:Benzothiazoles; D002232:Carbocyanines; D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D008244:Lysophosphatidylcholines; D008823:Micelles; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010715:Phosphatidylglycerols; D053835:Unilamellar Liposomes; C057561:1-palmitoyl-2-oleoylphosphatidylethanolamine; C006065:We 201; C012944:3,3'-dipropyl-2,2'-thiadicarbocyanine; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
keywords: Cell membrane; GA-K4 undecapeptide; Staphylococcus aereus; liposome; micelle; model membranes