Structural conservation in prokaryotic and eukaryotic potassium channels.
Toxins from scorpion venom interact with potassium channels. Resin-attached, mutant K+ channels from Streptomyces lividans were used to screen venom from Leiurus quinquestriatus hebraeus, and the toxins that interacted with the channel were rapidly identified by mass spectrometry. One of the toxins, agitoxin2, was further studied by mutagenesis and radioligand binding. The results show that a prokaryotic K+ channel has the same pore structure as eukaryotic K+ channels. This structural conservation, through application of techniques presented here, offers a new approach for K+ channel pharmacology.
MacKinnon
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R
Laboratory of Molecular Neurobiology and Biophysics and the Howard Hughes Medical Institute, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. mackinn@rockvax.rockefeller.edu
Cohen
S L
SL
Kuo
A
A
Lee
A
A
Chait
B T
BT
D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D001665:Binding Sites; D018999:Charybdotoxin / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017354:Point Mutation; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D011869:Radioligand Assay; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012604:Scorpion Venoms / Q000378:metabolism*; D016415:Sequence Alignment; D051637:Shaker Superfamily of Potassium Channels; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013302:Streptomyces / Q000737:chemistry
D001426:Bacterial Proteins; C106614:Lq2 protein, Leiurus quinquestriatus; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011994:Recombinant Proteins; D012604:Scorpion Venoms; D051637:Shaker Superfamily of Potassium Channels; C107790:prokaryotic potassium channel; D018999:Charybdotoxin; C087603:agitoxin 2