Hydramacin-1, structure and antibacterial activity of a protein from the basal metazoan Hydra.
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.
Jung
Sascha
S
Institute of Biochemistry and Institute of Zoology, Zoophysiology, Christian-Albrechts-University of Kiel, Olshausenstrasse 40, 24098 Kiel, Germany.
Dingley
Andrew J
AJ
Augustin
René
R
Anton-Erxleben
Friederike
F
Stanisak
Mareike
M
Gelhaus
Christoph
C
Gutsmann
Thomas
T
Hammer
Malte U
MU
Podschun
Rainer
R
Bonvin
Alexandre M J J
AM
Leippe
Matthias
M
Bosch
Thomas C G
TC
Grötzinger
Joachim
J
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
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D004220:Disulfides; D011506:Proteins; C539006:hydramacin-1, Hydra magnipapillata