IV. Na+ Selectivity
The helices of S5-6 form a loop within the channel's
transmembrane region, which serves a selective pore for Na+
ions.
Each of the four regions that make up the selectivity
filter contains one of a conserved series of amino acids, Asp-Glu-Lys-Ala (DEKA),
that
are responsible for Na+ ion selectivity. The location of
the DEKA residue in each repeat is termed the SF locus. The DEKA
motif is common among proteins with Na+ selectivity.
IV. Interactions with Toxins
The NaV1.7 ion channel includes several small openings that can
be penetrated by fatty acid chains.
This molecule is in complex with a small molecule called
saxitoxin. Saxitoxin (C10H17N7O4)
is a pore blocker, one of the two main classes of drugs and
toxins that target voltage-gated sodium channels.
Saxitoxin binds in the pore at a conserved location in VSDIII.
Specifically, Thr1409
and Ile1410 interact
with the toxin in the pore.
VI. References
Luo, L. (2016). Chapter 2 - Signaling
Within Neurons. Principles of Neurobiology. Garland
Science.
Tsai, C-J., Tani, K., Irie, K., Hiroaki,
Y., Shimomura, T., McMillan, DG., et al. (2013). Two
Alternative Conformations of a Voltage-Gated Sodium Channel. Journal
of Molecular Biology, 425(22), 4074-88.
Shen, H., Liu, D., Wu, K., Lei, J., and
Yan, N. (2019). Structures of human Nav1.7 channel in complex
with auxiliary subunits and animal toxins. Science,
363(6433), 1303–1308.
Shen, H., Zhou, Q., Pan, X., Li, Z., Wu,
J., and Yan, N. (2017). Structure of a eukaryotic
voltage-gated sodium channel at near-atomic resolution. Science,
355(6328).
Yu, F.H., Catterall, W.A. (2003).
Overview of the voltage-gated sodium channel family. Genome
Biol 4(207).
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