Solution Structure of ω-Grammotoxin SIA, A Gating Modifier of P/Q and N-type Ca2+ Channel
Solution Structure of ω-Grammotoxin SIA, A Gating Modifier of P/Q and N-type Ca2+ Channel
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DOI：
10.1016/s0022-2836(02)00595-8
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发表时间：
2002-08
影响因子：
5.6
通讯作者：
K. Takeuchi;E. Park;C. Lee;J. Kim;H. Takahashi;H. Takahashi;Kenton Jon Swartz;I. Shimada;I. Shimada
中科院分区：
文献类型：
--
作者：
K. Takeuchi;E. Park;C. Lee;J. Kim;H. Takahashi;H. Takahashi;Kenton Jon Swartz;I. Shimada;I. Shimada
ω-Grammotoxin SIA (GrTx) is a 36 amino acid residue protein toxin from spider venom that inhibits P/Q and N-type voltage-gated Ca2+channels by modifying voltage-dependent gating. We determined the three-dimensional structure of GrTx using NMR spectroscopy. The toxin adopts an “inhibitor cystine knot” motif composed of two β-strands (Leu19-Cys21 and Cys30-Trp32) and a β-bulge (Trp6, Gly7-Cys30) with a +2x, −1 topology, which are connected by four chain reversals. Although GrTx was originally identified as an inhibitor of voltage-gated Ca2+channel, it also binds to K+channels with lower affinity. A similar cross-reaction was observed for Hanatoxin1 (HaTx), which binds to the voltage-sensing domains of K+and Ca2+channels with different affinities. A detailed comparison of the GrTx and HaTx structures identifies a conserved face containing a large hydrophobic patch surrounded by positively charged residues. The slight differences in the surface shape, which result from the orientation of the surface aromatic residues and/or the distribution of the charged residues, may explain the differences in the binding affinity of these gating modifiers with different voltage-gated ion channels.
