title: Micelle bound structure and DNA interaction of brevinin-2-related peptide, an antimicrobial peptide derived from frog skin.
abstract: Brevinin-2-related peptide (BR-II), a novel antimicrobial peptide isolated from the skin of frog, Rana septentrionalis, shows a broad spectrum of antimicrobial activity with low haemolytic activity. It has also been shown to have antiviral activity, specifically to protect cells from infection by HIV-1. To understand the active conformation of the BR-II peptide in membranes, we have investigated the interaction of BR-II with the prokaryotic and eukaryotic membrane-mimetic micelles such as sodium dodecylsulfate (SDS) and dodecylphosphocholine (DPC), respectively. The interactions were studied using fluorescence and circular dichroism (CD) spectroscopy. Fluorescence experiments revealed that the N-terminus tryptophan residue of BR-II interacts with the hydrophobic core of the membrane mimicking micelles. The CD results suggest that interactions with membrane-mimetic micelles induce an α-helix conformation in BR-II. We have also determined the solution structures of BR-II in DPC and SDS micelles using NMR spectroscopy. The structural comparison of BR-II in the presence of SDS and DPC micelles showed significant conformational changes in the residues connecting the N-terminus and C-terminus helices. The ability of BR-II to bind DNA was elucidated by agarose gel retardation and fluorescence experiments. The structural differences of BR-II in zwitterionic versus anionic membrane mimics and the DNA binding ability of BR-II collectively contribute to the general understanding of the pharmacological specificity of this peptide towards prokaryotic and eukaryotic membranes and provide insights into its overall antimicrobial mechanism.
authors.affiliation: School of Applied Science, Republic Polytechnic, Singapore.
authors.forename: Susmita
authors.initials: S
authors.lastname: Bandyopadhyay
authors.forename: Boon Yee
authors.initials: BY
authors.lastname: Ng
authors.forename: Charmaine
authors.initials: C
authors.lastname: Chong
authors.forename: Ming Zhen
authors.initials: MZ
authors.lastname: Lim
authors.forename: Sonia Kiran
authors.initials: SK
authors.lastname: Gill
authors.forename: Ke Hui
authors.initials: KH
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Sivaraman
authors.forename: Chiradip
authors.initials: C
authors.lastname: Chatterjee
mesh_terms: D029845:Amphibian Proteins / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000378:metabolism; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008823:Micelles; D008958:Models, Molecular; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D011898:Ranidae / Q000378:metabolism; D012867:Skin / Q000737:chemistry; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D013050:Spectrometry, Fluorescence; D013501:Surface-Active Agents / Q000737:chemistry / Q000378:metabolism
chemical_list: D029845:Amphibian Proteins; D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D004268:DNA-Binding Proteins; D008051:Lipid Bilayers; D008823:Micelles; D013501:Surface-Active Agents; D010767:Phosphorylcholine; C078414:brevinin-2, Rana; D012967:Sodium Dodecyl Sulfate; C028810:dodecylphosphocholine; D004247:DNA
keywords: antimicrobial peptide; brevinin-2-related peptide; n-dodecylphosphocholine; pUC19 DNA; sodium dodecylsulfate; two-dimensional NMR