2WH9

Solution structure of GxTX-1E

2WH9 の概要

• エントリーDOI: 10.2210/pdb2wh9/pdb
• NMR情報: BMRB: 16960
• 分子名称: GUANGXITOXIN-1EGXTX-1E (1 entity in total)
• 機能のキーワード: membrane protein inhibitor, potassium channel inhibitor, ionic channel inhibitor, knottin
• 由来する生物種: PLESIOPHRICTUS GUANGXIENSIS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3958.68

構造登録者

Lee, S.K.,Jung, H.H.,Lee, J.Y.,Lee, C.W.,Kim, J.I. (登録日: 2009-05-02, 公開日: 2010-05-26, 最終更新日: 2024-11-06)

主引用文献

Lee, S.,Milescu, M.,Jung, H.H.,Lee, J.Y.,Bae, C.H.,Lee, C.W.,Kim, H.H.,Swartz, K.J.,Kim, J.I.
Solution Structure of Gxtx-1E, a High Affinity Tarantula Toxin Interacting with Voltage Sensors in Kv2.1 Potassium Channels.
Biochemistry, 49:5134-, 2010

PubMed Abstract: GxTX-1E is a neurotoxin recently isolated from Plesiophrictus guangxiensis venom that inhibits the Kv2.1 channel in pancreatic beta-cells. The sequence of the toxin is related to those of previously studied tarantula toxins that interact with the voltage sensors in Kv channels, and GxTX-1E interacts with the Kv2.1 channel with unusually high affinity, making it particularly useful for structural and mechanistic studies. Here we determined the three-dimensional solution structure of GxTX-1E using NMR spectroscopy and compared it to that of several related tarantula toxins. The molecular structure of GxTX-1E is similar to those of tarantula toxins that target voltage sensors in Kv channels in that it contains an ICK motif, composed of beta-strands, and contains a prominent cluster of solvent-exposed hydrophobic residues surrounded by polar residues. When compared with the structure of SGTx1, a toxin for which mutagenesis data are available, the residue compositions of the two toxins are distinct in regions that are critical for activity, suggesting that their modes of binding to voltage sensors may be different. Interestingly, the structural architecture of GxTX-1E is also similar to that of JZTX-III, a tarantula toxin that interacts with Kv2.1 with low affinity. The most striking structural differences between GxTX-1E and JZTX-III are found in the orientation between the first and second cysteine loops and the C-terminal region of the toxins, suggesting that these regions of GxTX-1E are responsible for its high affinity.

PubMed: 20509680
DOI: 10.1021/BI100246U

実験手法

SOLUTION NMR