+検索条件
-Structure paper
タイトル | Structural basis for the modulation of voltage-gated sodium channels by animal toxins. |
---|---|
ジャーナル・号・ページ | Science, Vol. 362, Issue 6412, Year 2018 |
掲載日 | 2018年10月19日 |
![]() | Huaizong Shen / Zhangqiang Li / Yan Jiang / Xiaojing Pan / Jianping Wu / Ben Cristofori-Armstrong / Jennifer J Smith / Yanni K Y Chin / Jianlin Lei / Qiang Zhou / Glenn F King / Nieng Yan / ![]() ![]() |
PubMed 要旨 | 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 ...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-Å and 3.2-Å 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. |
![]() | ![]() ![]() |
手法 | EM (単粒子) |
解像度 | 2.6 - 3.2 Å |
構造データ | EMDB-6995, PDB-6a90: |
化合物 | ![]() ChemComp-NAG: ![]() ChemComp-NA: ![]() ChemComp-PC1: ![]() ChemComp-9SL: ![]() ChemComp-HOH: ![]() ChemComp-9SR: |
由来 |
|
![]() | MEMBRANE PROTEIN/TOXIN / complex / sodium channel / toxin / MEMBRANE PROTEIN / MEMBRANE PROTEIN-TOXIN complex |