4jpz
From Proteopedia
Voltage-gated sodium channel 1.2 C-terminal domain in complex with FGF13U and Ca2+/calmodulin
Structural highlights
FunctionFGF13_HUMAN Microtubule-binding protein which directly binds tubulin and is involved in both polymerization and stabilization of microtubules. Through its action on microtubules, may participate to the refinement of axons by negatively regulating axonal and leading processes branching. Plays a crucial role in neuron polarization and migration in the cerebral cortex and the hippocampus.[1] May regulate voltage-gated sodium channels transport and function.[2] May also play a role in MAPK signaling.[3] Publication Abstract from PubMedCa(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. Structural analyses of Ca(2+)/CaM interaction with NaV channel C-termini reveal mechanisms of calcium-dependent regulation.,Wang C, Chung BC, Yan H, Wang HG, Lee SY, Pitt GS Nat Commun. 2014 Sep 18;5:4896. doi: 10.1038/ncomms5896. PMID:25232683[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Chung BC | Lee SY | Pitt GS | Wang C | Wang HG | Yan H
