title: Site-directed mutagenesis at histidines of aerolysin from Aeromonas hydrophila: a lipid planar bilayer study.
abstract: The role of histidine residues in the formation of channels by the cytolytic toxin aerolysin has been studied in planar lipid bilayers by substituting each of the six histidines in the native protein with asparagine. His341 or His186 mutants had the same channel-forming ability as native toxin, whereas the His332 and His121 mutants were less active. Mutations at His132 and His107, which interfere with the oligomerization of the toxin, drastically reduce pore formation. These findings support the conclusion that oligomerization of the toxin must precede channel formation, and that at least two of the six histidine residues are essential for this to occur. The aerolysin channel is a water-filled pore with an approximate diameter of 9.3 +/- 0.4 A.
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: H U
authors.initials: HU
authors.lastname: Wilmsen
authors.forename: J T
authors.initials: JT
authors.lastname: Buckley
authors.forename: F
authors.initials: F
authors.lastname: Pattus
mesh_terms: D016980:Aeromonas hydrophila / Q000235:genetics*; D001427:Bacterial Toxins / Q000235:genetics* / Q000378:metabolism; D002463:Cell Membrane Permeability; D004910:Erythrocyte Membrane / Q000378:metabolism; D005798:Genes, Bacterial; D006021:Glycophorins / Q000378:metabolism; D006460:Hemolysin Proteins / Q000235:genetics* / Q000378:metabolism; D006639:Histidine; D007473:Ion Channels / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D008051:Lipid Bilayers; D016297:Mutagenesis, Site-Directed; D052899:Pore Forming Cytotoxic Proteins; D013329:Structure-Activity Relationship; D015032:Zinc / Q000494:pharmacology
chemical_list: D001427:Bacterial Toxins; D006021:Glycophorins; D006460:Hemolysin Proteins; D007473:Ion Channels; D008051:Lipid Bilayers; D052899:Pore Forming Cytotoxic Proteins; C021091:staphylococcal alpha-toxin; D006639:Histidine; C032676:aerolysin; D015032:Zinc