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PDBsum entry 4l1d
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Membrane protein
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PDB id
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4l1d
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References listed in PDB file
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Key reference
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Title
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Crystal structure and molecular imaging of the nav channel β3 subunit indicates a trimeric assembly.
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Authors
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S.Namadurai,
D.Balasuriya,
R.Rajappa,
M.Wiemhöfer,
K.Stott,
J.Klingauf,
J.M.Edwardson,
D.Y.Chirgadze,
A.P.Jackson.
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Ref.
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J Biol Chem, 2014,
289,
10797-10811.
[DOI no: ]
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PubMed id
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Abstract
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The vertebrate sodium (Nav) channel is composed of an ion-conducting α subunit
and associated β subunits. Here, we report the crystal structure of the human
β3 subunit immunoglobulin (Ig) domain, a functionally important component of
Nav channels in neurons and cardiomyocytes. Surprisingly, we found that the β3
subunit Ig domain assembles as a trimer in the crystal asymmetric unit.
Analytical ultracentrifugation confirmed the presence of Ig domain monomers,
dimers, and trimers in free solution, and atomic force microscopy imaging also
detected full-length β3 subunit monomers, dimers, and trimers. Mutation of a
cysteine residue critical for maintaining the trimer interface destabilized both
dimers and trimers. Using fluorescence photoactivated localization microscopy,
we detected full-length β3 subunit trimers on the plasma membrane of
transfected HEK293 cells. We further show that β3 subunits can bind to more
than one site on the Nav 1.5 α subunit and induce the formation of α subunit
oligomers, including trimers. Our results suggest a new and unexpected role for
the β3 subunits in Nav channel cross-linking and provide new structural
insights into some pathological Nav channel mutations.
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