title: Hydramacin-1, structure and antibacterial activity of a protein from the basal metazoan Hydra.
abstract: Hydramacin-1 is a novel antimicrobial protein recently discovered during investigations of the epithelial defense of the ancient metazoan Hydra. The amino acid sequence of hydramacin-1 shows no sequence homology to any known antimicrobial proteins. Determination of the solution structure revealed that hydramacin-1 possesses a disulfide bridge-stabilized alphabeta motif. This motif is the common scaffold of the knottin protein fold. The structurally closest relatives are the scorpion oxin-like superfamily. Within this superfamily hydramacin-1 establishes a new family of proteins that all share antimicrobial activity. Hydramacin-1 is potently active against Gram-positive and Gram-negative bacteria including multi-resistant human pathogenic strains. It leads to aggregation of bacteria as an initial step of its bactericidal mechanism. Aggregated cells are connected via electron-dense contacts and adopt a thorn apple-like morphology. Analysis of the hydramacin-1 structure revealed an unusual distribution of amino acid side chains on the surface. A belt of positively charged residues is sandwiched by two hydrophobic areas. Based on this characteristic surface feature and on biophysical analysis of protein-membrane interactions, we propose a model that describes the aggregation effect exhibited by hydramacin-1.
authors.affiliation: Institute of Biochemistry and Institute of Zoology, Zoophysiology, Christian-Albrechts-University of Kiel, Olshausenstrasse 40, 24098 Kiel, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Jung
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dingley
authors.forename: René
authors.initials: R
authors.lastname: Augustin
authors.forename: Friederike
authors.initials: F
authors.lastname: Anton-Erxleben
authors.forename: Mareike
authors.initials: M
authors.lastname: Stanisak
authors.forename: Christoph
authors.initials: C
authors.lastname: Gelhaus
authors.forename: Thomas
authors.initials: T
authors.lastname: Gutsmann
authors.forename: Malte U
authors.initials: MU
authors.lastname: Hammer
authors.forename: Rainer
authors.initials: R
authors.lastname: Podschun
authors.forename: Alexandre M J J
authors.initials: AM
authors.lastname: Bonvin
authors.forename: Matthias
authors.initials: M
authors.lastname: Leippe
authors.forename: Thomas C G
authors.initials: TC
authors.lastname: Bosch
authors.forename: Joachim
authors.initials: J
authors.lastname: Grötzinger
mesh_terms: D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D006090:Gram-Negative Bacteria; D006094:Gram-Positive Bacteria; D006801:Humans; D006829:Hydra / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D004220:Disulfides; D011506:Proteins; C539006:hydramacin-1, Hydra magnipapillata