An inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean tarantula.
The Kv2.1 voltage-activated K+ channel, a Shab-related K+ channel isolated from rat brain, is insensitive to previously identified peptide inhibitors. We have isolated two peptides from the venom of a Chilean tarantula, G. spatulata, that inhibit the Kv2.1 K+ channel. The two peptides, hanatoxin1 (HaTx1) and hanatoxin2 (HaTx2) are unrelated in primary sequence to other K+ channel inhibitors. The activity of HaTx was verified by synthesizing it in a bacterial expression system. The concentration dependence for both the degree of inhibition at equilibrium (Kd = 42 nM) and the kinetics of inhibition (kon = 3.7 x 10(4) M-1s-1; koff = 1.3 x 10(-3) s-1), are consistent with a bimolecular reaction between HaTx and the Kv2.1 K+ channel. Shaker-related, Shaw-related, and eag K+ channels were relatively insensitive to HaTx, whereas a Shal-related K+ channel was sensitive. Regions outside the scorpion toxin binding site (S5-S6 linker) determine sensitivity to HaTx. HaTx introduces a new class of K+ channel inhibitors that will be useful probes for studying K+ channel structure and function.
Swartz
K J
KJ
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
MacKinnon
R
R
D018528:ATP-Binding Cassette Transporters; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000235:genetics; D004594:Electrophysiology; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D058619:Maltose-Binding Proteins; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000737:chemistry / Q000502:physiology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013111:Spider Venoms / Q000737:chemistry*
D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D058619:Maltose-Binding Proteins; D009004:Monosaccharide Transport Proteins; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011993:Recombinant Fusion Proteins; D013111:Spider Venoms; C096469:hanatoxin; C461599:maltose transport system, E coli