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6J8G

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

Summary for 6J8G
Entry DOI10.2210/pdb6j8g/pdb
EMDB information9781
DescriptorSodium channel subunit beta-2, Sodium channel protein type 9 subunit alpha, Sodium channel subunit beta-1, ... (6 entities in total)
Functional Keywordsvoltage-gated sodium channel, membrane protein
Biological sourceHomo sapiens (Human)
More
Total number of polymer chains3
Total formula weight282996.44
Authors
Shen, H.,Liu, D.,Lei, J.,Yan, N. (deposition date: 2019-01-19, release date: 2019-02-27, Last modification date: 2024-11-06)
Primary citationShen, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.2 Å)
Structure validation

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