@article{c7b354b61fcb4ebe91357ea578069278,
title = "Structural basis for the modulation of voltage-gated sodium channels by animal toxins",
abstract = "Animal toxins that modulate the activity of voltage-gated sodium (Nav) 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 Nav channel NavPaS bound to a gatingmodifier toxin Dc1a at 2.8 angstrom-resolution and in the presence of TTXor STX at 2.6-{\AA} and 3.2-{\AA} resolution, respectively. Dc1a inserts into the cleft between VSDII and the pore of NavPaS, 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 Nav channel drugs.",
author = "Huaizong Shen and Zhangqiang Li and Yan Jiang and Xiaojing Pan and Jianping Wu and Ben Cristofori-Armstrong and Smith, {Jennifer J.} and Chin, {Yanni K.Y.} and Jianlin Lei and Qiang Zhou and King, {Glenn F.} and Nieng Yan",
note = "Funding Information: This work was funded by the National Key Basic Research (973) Program (2015CB910101 to N.Y.) and the National Key R&D Program (2016YFA0500402 to N.Y. and 2016YFA0501100 to J.L.) from Ministry of Science and Technology of China, the National Natural Science Foundation of China (projects 31621092, 31630017, and 31611130036 to N.Y.), the Australian Research Council (DP160104411), and the Australian National Health and Medical Research Council (Principal Research Fellowship and Program Grant APP1072113 to G.F.K.). We thank the Tsinghua University Branch of China National Center for Protein Sciences (Beijing) for providing the cryo-EM facility support. We thank the computational facility support on the cluster of Bio-Computing Platform (Tsinghua University Branch of China National Center for Protein Sciences Beijing) and the {"}Explorer 100{"} cluster system of Tsinghua National Laboratory for Information Science and Technology. N.Y. is supported by the Shirley M. Tilghman endowed professorship from Princeton University. Publisher Copyright: {\textcopyright} 2017 The Author(s). Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",
year = "2018",
month = oct,
day = "19",
doi = "10.1126/science.aau2596",
language = "English",
volume = "362",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science (AAAS)",
number = "6412",
}