6J8H

Structure of human voltage-gated sodium channel Nav1.7 in complex with auxiliary beta subunits, huwentoxin-IV and saxitoxin (Y1755 down)

6J8H の概要

• エントリーDOI: 10.2210/pdb6j8h/pdb
• EMDBエントリー: 9781
• 分子名称: Sodium channel subunit beta-2, Sodium channel protein type 9 subunit alpha, Sodium channel subunit beta-1, ... (6 entities in total)
• 機能のキーワード: voltage-gated sodium channel, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 282996.44

構造登録者

Shen, H.,Liu, D.,Lei, J.,Yan, N. (登録日: 2019-01-19, 公開日: 2019-02-27, 最終更新日: 2024-10-09)

主引用文献

Shen, H.,Liu, D.,Wu, K.,Lei, J.,Yan, N.
Structures of human Nav1.7 channel in complex with auxiliary subunits and animal toxins.
Science, 363:1303-1308, 2019

PubMed Abstract: Voltage-gated sodium channel Na1.7 represents a promising target for pain relief. Here we report the cryo-electron microscopy structures of the human Na1.7-β1-β2 complex bound to two combinations of pore blockers and gating modifier toxins (GMTs), tetrodotoxin with protoxin-II and saxitoxin with huwentoxin-IV, both determined at overall resolutions of 3.2 angstroms. The two structures are nearly identical except for minor shifts of voltage-sensing domain II (VSD), whose S3-S4 linker accommodates the two GMTs in a similar manner. One additional protoxin-II sits on top of the S3-S4 linker in VSD The structures may represent an inactivated state with all four VSDs "up" and the intracellular gate closed. The structures illuminate the path toward mechanistic understanding of the function and disease of Na1.7 and establish the foundation for structure-aided development of analgesics.

PubMed: 30765606
DOI: 10.1126/science.aaw2493

実験手法

ELECTRON MICROSCOPY (3.2 Å)