title: Purification, characterization, and synthesis of an inward-rectifier K+ channel inhibitor from scorpion venom.
abstract: We have purified a protein inhibitor of an inward-rectifier K+ channel, ROMK1, from the venom of the scorpion Leiurus quinquestriatus var. hebraeus. The inhibitor is Lq2, a previously discovered blocker of voltage- and Ca2+-activated K+ channels. Mutations were made on the channel and the inhibitor, and the resulting effects were examined using an electrophysiological assay. The data show that Lq2 blocks the pore of ROMK1, and that the interaction surface on Lq2 is the same for binding to inward-rectifier, voltage-activated, or Ca2+-activated K+ channels. These findings support the notion that different classes of K+ channels have different gates but a similar K+-selective pore structure.
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Lu
authors.forename: R
authors.initials: R
authors.lastname: MacKinnon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015640:Ion Channel Gating / Q000187:drug effects; D051036:Large-Conductance Calcium-Activated Potassium Channels; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated; D024661:Potassium Channels, Inwardly Rectifying; D012604:Scorpion Venoms / Q000737:chemistry* / Q000302:isolation & purification*; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; C106614:Lq2 protein, Leiurus quinquestriatus; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D024661:Potassium Channels, Inwardly Rectifying; D012604:Scorpion Venoms