@article{168116,
  keywords = {Animals, Amino Acid Sequence, Cryoelectron Microscopy, Insect Proteins, Tetrodotoxin, Ion Channel Gating, Protein Domains, Periplaneta, voltage-gated sodium channels, Saxitoxin, Spider Venoms, Voltage-Gated Sodium Channel Blockers},
  author = {Huaizong Shen and Zhangqiang Li and Yan Jiang and Xiaojing Pan and Jianping Wu and Ben Cristofori-Armstrong and Jennifer Smith and Yanni Chin and Jianlin Lei and Qiang Zhou and Glenn King and Nieng Yan},
  title = {Structural basis for the modulation of voltage-gated sodium channels by animal toxins},
  abstract = {<p>Animal toxins that modulate the activity of voltage-gated sodium (Na) channels are broadly divided into two categories-pore blockers and gating modifiers. The pore blockers tetrodotoxin (TTX) and saxitoxin (STX) are responsible for puffer fish and shellfish poisoning in humans, respectively. Here, we present structures of the insect Na channel NaPaS bound to a gating modifier toxin Dc1a at 2.8 angstrom-resolution and in the presence of TTX or STX at 2.6-{\r A} and 3.2-{\r A} resolution, respectively. Dc1a inserts into the cleft between VSD and the pore of NaPaS, making key contacts with both domains. The structures with bound TTX or STX reveal the molecular details for the specific blockade of Na access to the selectivity filter from the extracellular side by these guanidinium toxins. The structures shed light on structure-based development of Na channel drugs.</p>
},
  year = {2018},
  journal = {Science},
  volume = {362},
  month = {10/2018},
  issn = {1095-9203},
  doi = {10.1126/science.aau2596},
  language = {eng},
}