View source for 6owv


==Crystal structure of a Human Cardiac Calsequestrin Filament==
<StructureSection load='6owv' size='340' side='right'caption='[[6owv]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6owv]] is a 1 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=6OWV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OWV 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]] 1.88&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6owv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6owv OCA], [https://pdbe.org/6owv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6owv RCSB], [https://www.ebi.ac.uk/pdbsum/6owv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6owv ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CASQ2_HUMAN CASQ2_HUMAN] Defects in CASQ2 are the cause of catecholaminergic polymorphic ventricular tachycardia type 2 (CPVT2) [MIM:[https://omim.org/entry/611938 611938]; also known as stress-induced polymorphic ventricular tachycardia (VTSIP). CPVT2 is an autosomal recessive form of arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death.<ref>PMID:17881003</ref> <ref>PMID:11704930</ref> <ref>PMID:15485681</ref> <ref>PMID:16908766</ref> <ref>PMID:18399795</ref> 
== Function ==
[https://www.uniprot.org/uniprot/CASQ2_HUMAN CASQ2_HUMAN] Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle. The release of calcium bound to calsequestrin through a calcium release channel triggers muscle contraction. The skeletal muscle isoform (CASQ1) binds around 80 Ca(2+) ions, while the cardiac isoform (CASQ2) binds approximately 60 Ca(2+) ions.<ref>PMID:17881003</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mutations in the calcium-binding protein calsequestrin cause the highly lethal familial arrhythmia catecholaminergic polymorphic ventricular tachycardia (CPVT). In vivo, calsequestrin multimerizes into filaments, but there is not yet an atomic-resolution structure of a calsequestrin filament. We report a crystal structure of a human cardiac calsequestrin filament with supporting mutational analysis and in vitro filamentation assays. We identify and characterize a new disease-associated calsequestrin mutation, S173I, that is located at the filament-forming interface, and further show that a previously reported dominant disease mutation, K180R, maps to the same surface. Both mutations disrupt filamentation, suggesting that disease pathology is due to defects in multimer formation. An ytterbium-derivatized structure pinpoints multiple credible calcium sites at filament-forming interfaces, explaining the atomic basis of calsequestrin filamentation in the presence of calcium. Our study thus provides a unifying molecular mechanism through which dominant-acting calsequestrin mutations provoke lethal arrhythmias.

The structure of a calsequestrin filament reveals mechanisms of familial arrhythmia.,Titus EW, Deiter FH, Shi C, Wojciak J, Scheinman M, Jura N, Deo RC Nat Struct Mol Biol. 2020 Oct 12. pii: 10.1038/s41594-020-0510-9. doi:, 10.1038/s41594-020-0510-9. PMID:33046906<ref>PMID:33046906</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6owv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Deiter FH]]
[[Category: Deo RC]]
[[Category: Jura N]]
[[Category: Shi C]]
[[Category: Titus EW]]