Structures of human Na v 1.7 channel in complex with auxiliary subunits and animal toxins

Huaizong Shen, Dongliang Liu, Kun Wu, Jianlin Lei, Nieng Yan

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

Voltage-gated sodium channel Na v 1.7 represents a promising target for pain relief. Here we report the cryo–electron microscopy structures of the human Na v 1.7-b1-b2 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 II ), 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 IV . 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 Na v 1.7 and establish the foundation for structure-aided development of analgesics.

Original languageEnglish (US)
Pages (from-to)1303-1308
Number of pages6
JournalScience
Volume363
Issue number6433
DOIs
StatePublished - Mar 22 2019

All Science Journal Classification (ASJC) codes

  • General

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