title: Ion selectivity of the anthrax toxin channel and its effect on protein translocation.
abstract: Anthrax toxin consists of three ∼ 85-kD proteins: lethal factor (LF), edema factor (EF), and protective antigen (PA). PA63 (the 63-kD, C-terminal portion of PA) forms heptameric channels ((PA63)7) in planar phospholipid bilayer membranes that enable the translocation of LF and EF across the membrane. These mushroom-shaped channels consist of a globular cap domain and a 14-stranded β-barrel stem domain, with six anionic residues lining the interior of the stem to form rings of negative charges. (PA63)7 channels are highly cation selective, and, here, we investigate the effects on both cation selectivity and protein translocation of mutating each of these anionic residues to a serine. We find that although some of these mutations reduce cation selectivity, selectivity alone does not directly predict the rate of protein translocation; local changes in electrostatic forces must be considered as well.
authors.affiliation: Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461 avivaschiffmiller@gmail.com.
authors.forename: Aviva
authors.initials: A
authors.lastname: Schiffmiller
authors.affiliation: Acumenta Biotech, Westminster, MA 01473.
authors.forename: Damon
authors.initials: D
authors.lastname: Anderson
authors.affiliation: Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461.
authors.forename: Alan
authors.initials: A
authors.lastname: Finkelstein
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011188:Potassium / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D008051:Lipid Bilayers; C030325:anthrax toxin; D011188:Potassium