Structure and membrane interactions of the homodimeric antibiotic peptide homotarsinin

• DOI: 10.1038/srep40854
• Publication Date: 2017-01-19T14:10:29Z
• Authors: Rodrigo M. Verly; Jarbas M. Resende; Eduardo F. C. Junior; Mariana T. Q. de ...; Carlos F. C. R. G...; Victor H. O. Munhoz; Marcelo Porto Bem...; Fábio C. L. Almeida; Marcelo M. Santoro; Dorila Piló-Veloso; Burkhard Bechinger
• Keywords: 0301 basic medicine; Circular Dichroism; Lipid Bilayers; Microbial Sensitivity Tests; Calorimetry; Gram-Positive Bacteria; Article; Dynamic Light Scattering; Protein Structure, Tertiary; 03 medical and health sciences; Gram-Negative Bacteria; Animals; Amino Acid Sequence; Anura; Dimerization; Nuclear Magnetic Resonance, Biomolecular; Antimicrobial Cationic Peptides

AbstractAntimicrobial peptides (AMPs) from amphibian skin are valuable template structures to find new treatments against bacterial infections. This work describes for the first time the structure and membrane interactions of a homodimeric AMP. Homotarsinin, which was found in Phyllomedusa tarsius anurans, consists of two identical cystine-linked polypeptide chains each of 24 amino acid residues. The high-resolution structures of the monomeric and dimeric peptides were determined in aqueous buffers. The dimer exhibits a tightly packed coiled coil three-dimensional structure, keeping the hydrophobic residues screened from the aqueous environment. An overall cationic surface of the dimer assures enhanced interactions with negatively charged membranes. An extensive set of biophysical data allowed us to establish structure-function correlations with antimicrobial assays against Gram-positive and Gram-negative bacteria. Although both peptides present considerable antimicrobial activity, the dimer is significantly more effective in both antibacterial and membrane biophysical assays.