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PDBsum entry 4jpz
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Transport protein
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PDB id
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4jpz
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Contents |
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148 a.a.
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142 a.a.
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143 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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Structural analyses of ca²⁺/cam interaction with nav channel c-Termini reveal mechanisms of calcium-Dependent regulation.
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Authors
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C.Wang,
B.C.Chung,
H.Yan,
H.G.Wang,
S.Y.Lee,
G.S.Pitt.
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Ref.
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Nat Commun, 2014,
5,
4896.
[DOI no: ]
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PubMed id
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Abstract
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Ca(2+) regulates voltage-gated Na(+) (NaV) channels, and perturbed Ca(2+)
regulation of NaV function is associated with epilepsy syndromes, autism and
cardiac arrhythmias. Understanding the disease mechanisms, however, has been
hindered by a lack of structural information and competing models for how Ca(2+)
affects NaV channel function. Here we report the crystal structures of two
ternary complexes of a human NaV cytosolic C-terminal domain (CTD), a fibroblast
growth factor homologous factor and Ca(2+)/calmodulin (Ca(2+)/CaM). These
structures rule out direct binding of Ca(2+) to the NaV CTD and uncover new
contacts between CaM and the NaV CTD. Probing these new contacts with
biochemical and functional experiments allows us to propose a mechanism by which
Ca(2+) could regulate NaV channels. Further, our model provides hints towards
understanding the molecular basis of the neurologic disorders and cardiac
arrhythmias caused by NaV channel mutations.
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