title: Agitoxin footprinting the shaker potassium channel pore.
abstract: In voltage-dependent K+ channels, each of the four identical subunits contributes one pore loop to the central ion selectivity unit at the interface between the subunits. The pore loop is also the target for scorpion venom peptide inhibitors. These inhibitors bind at the pore entryway between the four subunits and can assume any one of four orientations. The orientations become distinguishable only if the binding site symmetry is disrupted. We have used mutagenesis and site-directed chemical modification to alter pore loop amino acids in either one or four subunits. The effects of these alterations on inhibitor affinity define the eccentricity of amino acids in the pore entryway and imply a different secondary structure for the amino and carboxyl ends of the pore loop.
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: A
authors.initials: A
authors.lastname: Gross
authors.forename: R
authors.initials: R
authors.lastname: MacKinnon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003545:Cysteine / Q000096:biosynthesis; D018983:DNA Footprinting; D004330:Drosophila / Q000235:genetics*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics*; D012604:Scorpion Venoms / Q000378:metabolism / Q000494:pharmacology*; D014118:Toxins, Biological / Q000378:metabolism / Q000494:pharmacology*; D014981:Xenopus
chemical_list: D015221:Potassium Channels; D012604:Scorpion Venoms; D014118:Toxins, Biological; C087603:agitoxin 2; D003545:Cysteine