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PDBsum entry 4ovn
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Metal binding protein
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PDB id
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4ovn
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References listed in PDB file
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Key reference
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Title
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Regulation of the nav1.5 cytoplasmic domain by calmodulin.
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Authors
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S.B.Gabelli,
A.Boto,
V.H.Kuhns,
M.A.Bianchet,
F.Farinelli,
S.Aripirala,
J.Yoder,
J.Jakoncic,
G.F.Tomaselli,
L.M.Amzel.
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Ref.
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Nat Commun, 2014,
5,
5126.
[DOI no: ]
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PubMed id
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Abstract
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Voltage-gated sodium channels (Na(v)) underlie the rapid upstroke of action
potentials in excitable tissues. Binding of channel-interactive proteins is
essential for controlling fast and long-term inactivation. In the structure of
the complex of the carboxy-terminal portion of Na(v)1.5 (CTNa(v)1.5) with
calmodulin (CaM)-Mg(2+) reported here, both CaM lobes interact with the
CTNa(v)1.5. On the basis of the differences between this structure and that of
an inactivated complex, we propose that the structure reported here represents a
non-inactivated state of the CTNa(v), that is, the state that is poised for
activation. Electrophysiological characterization of mutants further supports
the importance of the interactions identified in the structure. Isothermal
titration calorimetry experiments show that CaM binds to CTNa(v)1.5 with high
affinity. The results of this study provide unique insights into the
physiological activation and the pathophysiology of Na(v) channels.
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