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PDBsum entry 6j8h
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Membrane protein
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PDB id
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6j8h
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Contents |
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120 a.a.
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1140 a.a.
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173 a.a.
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References listed in PDB file
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Key reference
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Title
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Structures of human naV1.7 channel in complex with auxiliary subunits and animal toxins.
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Authors
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H.Shen,
D.Liu,
K.Wu,
J.Lei,
N.Yan.
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Ref.
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Science, 2019,
363,
1303-1308.
[DOI no: ]
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PubMed id
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Abstract
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Voltage-gated sodium channel Nav1.7 represents a promising target for
pain relief. Here we report the cryo-electron microscopy structures of the human
Nav1.7-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 (VSDII), 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
VSDIV 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
Nav1.7 and establish the foundation for structure-aided development
of analgesics.
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