title: Structure and membrane interactions of the homodimeric antibiotic peptide homotarsinin.
abstract: Antimicrobial 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.
authors.affiliation: Departamento de Química Universidade Federal de Minas Gerais, P.O.Box 486, 31270-901 Belo Horizonte, MG, Brazil.|Departamento de Química Universidade Federal dos Vales do Jequitinhonha e Mucuri, 39100-000 Diamantina, MG, Brazil.
authors.forename: Rodrigo M
authors.initials: RM
authors.lastname: Verly
authors.affiliation: Departamento de Química Universidade Federal de Minas Gerais, P.O.Box 486, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Jarbas M
authors.initials: JM
authors.lastname: Resende
authors.affiliation: Departamento de Química Universidade Federal dos Vales do Jequitinhonha e Mucuri, 39100-000 Diamantina, MG, Brazil.
authors.forename: Eduardo F C
authors.initials: EF
authors.lastname: Junior
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, P.O.Box 486, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Mariana T Q
authors.initials: MT
authors.lastname: de Magalhães
authors.affiliation: Departamento de Química Universidade Federal de Minas Gerais, P.O.Box 486, 31270-901 Belo Horizonte, MG, Brazil.|Departamento de Química Universidade Federal dos Vales do Jequitinhonha e Mucuri, 39100-000 Diamantina, MG, Brazil.
authors.forename: Carlos F C R
authors.initials: CF
authors.lastname: Guimarães
authors.affiliation: Departamento de Química Universidade Federal de Minas Gerais, P.O.Box 486, 31270-901 Belo Horizonte, MG, Brazil.|Departamento de Química Universidade Federal dos Vales do Jequitinhonha e Mucuri, 39100-000 Diamantina, MG, Brazil.
authors.forename: Victor H O
authors.initials: VH
authors.lastname: Munhoz
authors.affiliation: Laboratório de Espectrometria de Massa, Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA) - Recursos Genéticos e Biotecnologia, Estação Parque Biológico, Final W5, Asa Norte, Brasília, DF, 70770-900, Brazil.
authors.forename: Marcelo Porto
authors.initials: MP
authors.lastname: Bemquerer
authors.affiliation: Centro Nacional de Ressonância Magnética Nuclear Jiri Jonas - CNRMN, Instituto de Bioquimica Médica, Programa de Biologia Estrutural, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Fábio C L
authors.initials: FC
authors.lastname: Almeida
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, P.O.Box 486, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Santoro
authors.affiliation: Departamento de Química Universidade Federal de Minas Gerais, P.O.Box 486, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Dorila
authors.initials: D
authors.lastname: Piló-Veloso
authors.affiliation: Université de Strasbourg/CNRS, UMR7177, Institut de Chimie, Strasbourg, France.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Bechinger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001001:Anura / Q000378:metabolism; D002151:Calorimetry; D002942:Circular Dichroism; D019281:Dimerization; D000067493:Dynamic Light Scattering; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D019906:Nuclear Magnetic Resonance, Biomolecular; D017434:Protein Structure, Tertiary
chemical_list: D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; C000628703:homotarsinin