1LA4

Solution Structure of SGTx1

1LA4 の概要

• エントリーDOI: 10.2210/pdb1la4/pdb
• 分子名称: SGTx1 (1 entity in total)
• 機能のキーワード: triple-stranded antiparallel beta-sheet, inhibitory cystine knot, peptide neurotoxin, toxin
• 細胞内の位置: Secreted: P56855
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3788.36

構造登録者

Lee, C.W.,Roh, S.H.,Kim, S.,Endoh, H.,Kodera, Y.,Maeda, T.,Swartz, K.J.,Kim, J.I. (登録日: 2002-03-28, 公開日: 2003-11-11, 最終更新日: 2024-10-23)

主引用文献

Lee, C.W.,Kim, S.,Roh, S.H.,Endoh, H.,Kodera, Y.,Maeda, T.,Kohno, T.,Wang, J.M.,Swartz, K.J.,Kim, J.I.
Solution Structure and Functional Characterization of SGTx1, a Modifier of Kv2.1 Channel Gating
Biochemistry, 43:890-897, 2004

PubMed Abstract: SGTx1 is a peptide toxin isolated from the venom of the spider Scodra griseipes that has been shown to inhibit outward K(+) currents in rat cerebellar granule neurons. Although its amino acid sequence is known to be highly (76%) homologous with that of hanatoxin (HaTx), a well-characterized modifier of Kv2.1 channel gating, the structural and functional characteristics of SGTx1 remain largely unknown. Here we describe the NMR solution structure of SGTx1, the mechanism of its interaction with Kv2.1 channels, and its effect on channel activity once bound. The NMR structure of SGTx1 contains a molecular fold closely resembling the "inhibitor cystine knot" of HaTx, which is composed of an antiparallel beta-sheet and four chain reversals stabilized by three disulfide bonds. Functionally, SGTx1 reversibly inhibited K(+) currents in oocytes expressing Kv2.1 channels. Moreover, generation of steady-state activation curves showed that, consistent with other gating modifiers, SGTx1 acted by shifting the activation of the channel to more depolarized voltages. Thus, the surface profile and mechanism of action of SGTx1 are similar to those of HaTx. Still, detailed comparison of SGTx1 with HaTx revealed differences in binding affinity and conformational homogeneity that result from differences in the charge distribution at the binding surface and in the amino acid composition of the respective beta-hairpin structures in the peptides.

PubMed: 14744131
DOI: 10.1021/bi0353373

実験手法

SOLUTION NMR