• SyncroPatch 384/768i

    世界最速のオートパッチ
  • SyncroPatch 384/768i

    384ch同時測定 => 768chへアップグレード可能
  • SyncroPatch 384/768i

    ギガシールによるHTS
  • SyncroPatch 384/768i

    Analysis Software even more powerful than before
  • SyncroPatch 384/768i

    最先端技術によるアッセイ柔軟性

2019 - Structural Basis of Nav1.7 Inhibition by a Gating-Modifier Spider Toxin

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Cell (2019)

Authors:
Xu H., Li T., Rohou A., Arthur C.P., Tzakoniati F., Wong E., Estevez A., Kugel C., Franke Y., Chen J., Ciferri C., Hackos D.H., Koth C.M., Payandeh J.

Journal:
Cell (2019) doi: 10.1016/j.cell.2018.12.018.


Abstract:

Voltage-gated sodium (Nav) channels are targets of disease mutations, toxins, and therapeutic drugs. Despite recent advances, the structural basis of voltage sensing, electromechanical coupling, and toxin modulation remains ill-defined. Protoxin-II (ProTx2) from the Peruvian green velvet tarantula is an inhibitor cystine-knot peptide and selective antagonist of the human Nav1.7 channel. Here, we visualize ProTx2 in complex with voltage-sensor domain II (VSD2) from Nav1.7 using X-ray crystallography and cryoelectron microscopy. Membrane partitioning orients ProTx2 for unfettered access to VSD2, where ProTx2 interrogates distinct features of the Nav1.7 receptor site. ProTx2 positions two basic residues into the extracellular vestibule to antagonize S4 gating-charge movement through an electrostatic mechanism. ProTx2 has trapped activated and deactivated states of VSD2, revealing a remarkable ∼10 Å translation of the S4 helix, providing a structural framework for activation gating in voltage-gated ion channels. Finally, our results deliver key templates to design selective Nav channel antagonists.


Download here

Back

SyncroPatch 384i brochure

Cookies make it easier for us to provide you with our services. With the usage of our services you permit us to use cookies.
More information Ok