6mc9: Difference between revisions

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-'''Unreleased structure'''
-The entry 6mc9 is ON HOLD
+==Crystal Structure of Human Nav1.4 C-Terminal (1599-1754) domain in complex with calcium-bound calmodulin==
+<StructureSection load='6mc9' size='340' side='right'caption='[[6mc9]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6mc9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MC9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MC9 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3&#8491;</td></tr>
+<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>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6mc9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mc9 OCA], [https://pdbe.org/6mc9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mc9 RCSB], [https://www.ebi.ac.uk/pdbsum/6mc9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mc9 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/SCN4A_HUMAN SCN4A_HUMAN] Postsynaptic congenital myasthenic syndromes;Paramyotonia congenita of Von Eulenburg;Myotonia fluctuans;Hyperkalemic periodic paralysis;Acetazolamide-responsive myotonia;Myotonia permanens;Hypokalemic periodic paralysis. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  SCN4A mutations are the cause of an autosomal recessive neuromuscular disorder characterized by severe fetal hypokinesia, neonatal hypotonia and congenital myopathy of variable severity. The most severe clinical features include reduced or absent fetal movements, in-utero upper and lower limb contractures, talipes and hydrops, and intrauterine or early postnatal death. Mildly affected patients present with generalized hypotonia and weakness at birth or within the first few days of life, mild-to-moderate facial muscle weakness without ptosis, significant early respiratory and feeding difficulties, and skeletal abnormalities of the spine and palate. Symptoms improve over time in patients who survive infancy, resulting in gain of muscle strength and motor skills and concomitant resolution of early respiratory and feeding difficulties. In contrast to other SCN4A-related channelopathies, affected individuals manifest in-utero or neonatal onset of permanent muscle weakness, rather than later-onset episodic muscle weakness.<ref>PMID:26700687</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/SCN4A_HUMAN SCN4A_HUMAN] This protein 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. This sodium channel may be present in both denervated and innervated skeletal muscle.<ref>PMID:15318338</ref> <ref>PMID:16890191</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Skeletal muscle voltage-gated Na(+) channel (NaV1.4) activity is subject to calmodulin (CaM) mediated Ca(2+)-dependent inactivation; no such inactivation is observed in the cardiac Na(+) channel (NaV1.5). Taken together, the crystal structures of the NaV1.4 C-terminal domain relevant complexes and thermodynamic binding data presented here provide a rationale for this isoform difference. A Ca(2+)-dependent CaM N-lobe binding site previously identified in NaV1.5 is not present in NaV1.4 allowing the N-lobe to signal other regions of the NaV1.4 channel. Consistent with this mechanism, removing this binding site in NaV1.5 unveils robust Ca(2+)-dependent inactivation in the previously insensitive isoform. These findings suggest that Ca(2+)-dependent inactivation is effected by CaM's N-lobe binding outside the NaV C-terminal while CaM's C-lobe remains bound to the NaV C-terminal. As the N-lobe binding motif of NaV1.5 is a mutational hotspot for inherited arrhythmias, the contributions of mutation-induced changes in CDI to arrhythmia generation is an intriguing possibility.
-Authors: Yoder, J.B., Gabelli, S.B., Amzel, L.M.
+Ca(2+)-dependent regulation of sodium channels NaV1.4 and NaV1.5 is controlled by the post-IQ motif.,Yoder JB, Ben-Johny M, Farinelli F, Srinivasan L, Shoemaker SR, Tomaselli GF, Gabelli SB, Amzel LM Nat Commun. 2019 Apr 3;10(1):1514. doi: 10.1038/s41467-019-09570-7. PMID:30944319<ref>PMID:30944319</ref>
-Description: Crystal Structure of Human Nav1.4 C-Terminal (1599-1754) domain in complex with calcium-bound calmodulin
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Gabelli, S.B]]
+<div class="pdbe-citations 6mc9" style="background-color:#fffaf0;"></div>
-[[Category: Yoder, J.B]]
-[[Category: Amzel, L.M]]
+==See Also==
+*[[Calmodulin 3D structures|Calmodulin 3D structures]]
+*[[Ion channels 3D structures|Ion channels 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Rattus norvegicus]]
+[[Category: Amzel LM]]
+[[Category: Gabelli SB]]
+[[Category: Yoder JB]]