2N9Z

Solution structure of K1 lobe of double-knot toxin

2N9Z の概要

• エントリーDOI: 10.2210/pdb2n9z/pdb
• NMR情報: BMRB: 25922
• 分子名称: Tau-theraphotoxin-Hs1a (1 entity in total)
• 機能のキーワード: trpv1, tarantula, spider, ick, double-knot toxin, dktx, k1, toxin
• 由来する生物種: Haplopelma schmidti (Chinese earth tiger)
• 細胞内の位置: Secreted: P0CH43
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4884.71

構造登録者

Bae, C.,Anselmi, C.,Kalia, J.,Jara-Oseguera, A.,Schwieters, C.D.,Krepkiy, D.,Lee, C.W.,Kim, E.H.,Kim, J.I.,Faraldo-Gomez, J.D.,Swartz, K.J. (登録日: 2015-12-16, 公開日: 2016-03-02, 最終更新日: 2024-11-20)

主引用文献

Bae, C.,Anselmi, C.,Kalia, J.,Jara-Oseguera, A.,Schwieters, C.D.,Krepkiy, D.,Lee, C.W.,Kim, E.H.,Kim, J.I.,Faraldo-Gomez, J.D.,Swartz, K.J.
Structural insights into the mechanism of activation of the TRPV1 channel by a membrane-bound tarantula toxin
Elife, 5:-, 2016

PubMed Abstract: Venom toxins are invaluable tools for exploring the structure and mechanisms of ion channels. Here, we solve the structure of double-knot toxin (DkTx), a tarantula toxin that activates the heat-activated TRPV1 channel. We also provide improved structures of TRPV1 with and without the toxin bound, and investigate the interactions of DkTx with the channel and membranes. We find that DkTx binds to the outer edge of the external pore of TRPV1 in a counterclockwise configuration, using a limited protein-protein interface and inserting hydrophobic residues into the bilayer. We also show that DkTx partitions naturally into membranes, with the two lobes exhibiting opposing energetics for membrane partitioning and channel activation. Finally, we find that the toxin disrupts a cluster of hydrophobic residues behind the selectivity filter that are critical for channel activation. Collectively, our findings reveal a novel mode of toxin-channel recognition that has important implications for the mechanism of thermosensation.

PubMed: 26880553
DOI: 10.7554/eLife.11273

実験手法

SOLUTION NMR