Solution structure of hanatoxin1, a gating modifier of voltage-dependent K+ channels: Common surface features of gating modifier toxins

The three-dimensional structure of hanatoxin1 (HaTx1) was determined by usi ng NMR spectroscopy. HaTx1 is a 35 amino acid residue peptide toxin that in hibits the drk1 voltage-gated K+ channel not by blocking the pore, but by a ltering the energetics of gating. both the amino acid sequence of HaTx1 and its unique mechanism of action distinguish this toxin from the previously described K+ channel inhibitors. Unlike most other K+ channel-blocking toxi ns, HaTx1 adopts an "inhibitor cystine knot" motif and is composed of two b eta-strands, strand I for residues 19-21 and strand II for residues 28-30, connected by four chain reversals. A comparison of the surface features of HaTx1 with those of other gating modifier toxins of voltage-gated Ca2+ and Na+ channels suggests that the combination of a hydrophobic patch and surro unding charged residues is principally responsible for the binding of gatin g modifier toxins to voltage-gated ion channels. (C) 2000 Academic Press.