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Papers of the Week

Papers: 16 Feb 2019 - 22 Feb 2019

Animal Studies, Human Studies, Pharmacology/Drug Development

2019 Mar 22




Editor's Pick

Structures of human Na1.7 channel in complex with auxiliary subunits and animal toxins.


Shen H, Liu D, Wu K, Lei J, Yan N
Science. 2019 Mar 22; 363(6433):1303-1308.
PMID: 30765606.


Voltage-gated sodium channel Na1.7 represents a promising target for pain relief. Here we report the cryo-EM 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 Å. The two structures are nearly identical except for minor shifts of 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.