Title:Cellular Membrane Composition Requirement by Antimicrobial and Anticancer Peptide GA-K4
Volume: 24
Issue: 3
Author(s): Tsogbadrakh Mishig-Ochir, Davaadulam Gombosuren, Altanchimeg Jigjid, Badamkhatan Tuguldur, Galbadrakh Chuluunbaatar, Enerelt Urnukhsaikhan, Chinar Pathak and Bong-Jin Lee
Affiliation:
Keywords:
Cell membrane, GA-K4 undecapeptide, liposome, micelle, model membranes, Staphylococcus aereus.
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.
