4jq0 | pdb_00004jq0

Voltage-gated sodium channel 1.5 C-terminal domain in complex with FGF12B and Ca2+/calmodulin

spinqualitylabelsall models 4jq0, resolution 3.84Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4jq0 is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FGF12_HUMAN Probably involved in nervous system development and function. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Calmodulin 3D structures Fibroblast growth factor 3D structures Ion channels 3D structures

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