4jpz

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==Voltage-gated sodium channel 1.2 C-terminal domain in complex with FGF13U and Ca2+/calmodulin==
==Voltage-gated sodium channel 1.2 C-terminal domain in complex with FGF13U and Ca2+/calmodulin==
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<StructureSection load='4jpz' size='340' side='right' caption='[[4jpz]], [[Resolution|resolution]] 3.02&Aring;' scene=''>
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<StructureSection load='4jpz' size='340' side='right'caption='[[4jpz]], [[Resolution|resolution]] 3.02&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4jpz]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JPZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JPZ FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4jpz]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JPZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JPZ FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.02&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jq0|4jq0]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FGF13, FHF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SCN2A, NAC2, SCN2A1, SCN2A2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CALM1, CALM, CAM, CAM1, CALM2, CAM2, CAMB, CALM3, CALML2, CAM3, CAMC, CAMIII ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4jpz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jpz OCA], [https://pdbe.org/4jpz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jpz RCSB], [https://www.ebi.ac.uk/pdbsum/4jpz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jpz ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jpz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jpz OCA], [http://pdbe.org/4jpz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jpz RCSB], [http://www.ebi.ac.uk/pdbsum/4jpz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jpz ProSAT]</span></td></tr>
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</table>
</table>
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== Disease ==
 
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[[http://www.uniprot.org/uniprot/SCN2A_HUMAN SCN2A_HUMAN]] Defects in SCN2A are the cause of seizures, benign familial infantile type 3 (BFIS3) [MIM:[http://omim.org/entry/607745 607745]]. An autosomal dominant disorder in which afebrile seizures occur in clusters during the first year of life, without neurologic sequelae.<ref>PMID:11371648</ref> <ref>PMID:12243921</ref> <ref>PMID:15048894</ref> <ref>PMID:20371507</ref> Defects in SCN2A are the cause of epileptic encephalopathy early infantile type 11 (EIEE11) [MIM:[http://omim.org/entry/613721 613721]]. EIEE11 is an autosomal dominant seizure disorder characterized by infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities.<ref>PMID:19786696</ref> <ref>PMID:20956790</ref>
 
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/FGF13_HUMAN FGF13_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.<ref>PMID:15282281</ref> May regulate voltage-gated sodium channels transport and function.<ref>PMID:15282281</ref> May also play a role in MAPK signaling.<ref>PMID:15282281</ref> [[http://www.uniprot.org/uniprot/SCN2A_HUMAN SCN2A_HUMAN]] Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
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[https://www.uniprot.org/uniprot/FGF13_HUMAN FGF13_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.<ref>PMID:15282281</ref> May regulate voltage-gated sodium channels transport and function.<ref>PMID:15282281</ref> May also play a role in MAPK signaling.<ref>PMID:15282281</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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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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<ref>PMID:25232683</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4jpz" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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*[[Calmodulin|Calmodulin]]
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*[[Calmodulin 3D structures|Calmodulin 3D structures]]
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*[[Ion channels|Ion channels]]
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*[[Fibroblast growth factor 3D structures|Fibroblast growth factor 3D structures]]
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*[[Ion channels 3D structures|Ion channels 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Chung, B C]]
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[[Category: Large Structures]]
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[[Category: Lee, S Y]]
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[[Category: Chung BC]]
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[[Category: Pitt, G S]]
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[[Category: Lee SY]]
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[[Category: Wang, C]]
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[[Category: Pitt GS]]
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[[Category: Wang, H G]]
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[[Category: Wang C]]
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[[Category: Yan, H]]
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[[Category: Wang HG]]
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[[Category: Ef hand and iq motif]]
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[[Category: Yan H]]
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[[Category: Ion channel]]
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[[Category: Membrane]]
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[[Category: Transport protein]]
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Current revision

Voltage-gated sodium channel 1.2 C-terminal domain in complex with FGF13U and Ca2+/calmodulin

PDB ID 4jpz

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