1d1h
From Proteopedia
SOLUTION STRUCTURE OF HANATOXIN 1
Structural highlights
FunctionTXHN1_GRARO Inhibits Kv2.1/KCNB1 and Kv4.2/KCND2 voltage-gated potassium channels. Acts as a gating modifier by shifting channel openings to more depolarized voltages and acts via the occupancy of multiple binding sites on the channel. The toxin binding sites are situated on the S3-S4 extracellular linker of the channel. At least two hanatoxin molecules can occupy the Kv2.1/KCNB1 channel, and maybe more (three or four). Can also inhibit calcium channels (Cav2.1/CACNA1A). Needs to partition into the membrane in order to bind to the channel.[1] [2] [3] [4] Publication Abstract from PubMedThe three-dimensional structure of hanatoxin1 (HaTx1) was determined by using NMR spectroscopy. HaTx1 is a 35 amino acid residue peptide toxin that inhibits the drk1 voltage-gated K(+) channel not by blocking the pore, but by altering 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 toxins, HaTx1 adopts an "inhibitor cystine knot" motif and is composed of two beta-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 Ca(2+) and Na(+) channels suggests that the combination of a hydrophobic patch and surrounding charged residues is principally responsible for the binding of gating modifier toxins to voltage-gated ion channels. Solution structure of hanatoxin1, a gating modifier of voltage-dependent K(+) channels: common surface features of gating modifier toxins.,Takahashi H, Kim JI, Min HJ, Sato K, Swartz KJ, Shimada I J Mol Biol. 2000 Mar 31;297(3):771-80. PMID:10731427[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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