View source for 6xxf


==1.7 Angstrom crystal structure of Ca/CaM:RyR2 peptide complex==
<StructureSection load='6xxf' size='340' side='right'caption='[[6xxf]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6xxf]] is a 2 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=6XXF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XXF 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]] 1.7&#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=6xxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xxf OCA], [https://pdbe.org/6xxf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xxf RCSB], [https://www.ebi.ac.uk/pdbsum/6xxf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xxf ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CALM2_HUMAN CALM2_HUMAN] Catecholaminergic polymorphic ventricular tachycardia;Brugada syndrome;Romano-Ward syndrome. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM2 are the cause of LQT15.
== Function ==
[https://www.uniprot.org/uniprot/CALM2_HUMAN CALM2_HUMAN] Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).<ref>PMID:16760425</ref> <ref>PMID:26969752</ref> <ref>PMID:27165696</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited condition that can cause fatal cardiac arrhythmia. Human mutations in the Ca2+ sensor calmodulin (CaM) have been associated with CPVT susceptibility, suggesting that CaM dysfunction is a key driver of the disease. However, the detailed molecular mechanism remains unclear. Focusing on the interaction with the cardiac ryanodine receptor (RyR2), we determined the effect of CPVT-associated variants N53I and A102V on the structural characteristics of CaM and on Ca2+ fluxes in live cells. We provide novel data showing that interaction of both Ca2+/CaM-N53I and Ca2+/CaM-A102V with the RyR2 binding domain is decreased. Ca2+/CaM-RyR23583-3603 high-resolution crystal structures highlight subtle conformational changes for the N53I variant, with A102V being similar to wild type (WT). We show that co-expression of CaM-N53I or CaM-A102V with RyR2 in HEK293 cells significantly increased the duration of Ca2+ events; CaM-A102V exhibited a lower frequency of Ca2+ oscillations. In addition, we show that CaMKIIdelta (also known as CAMK2D) phosphorylation activity is increased for A102V, compared to CaM-WT. This paper provides novel insight into the molecular mechanisms of CPVT-associated CaM variants and will facilitate the development of strategies for future therapies.

CPVT-associated calmodulin variants N53I and A102V dysregulate Ca2+ signalling via different mechanisms.,Prakash O, Held M, McCormick LF, Gupta N, Lian LY, Antonyuk S, Haynes LP, Thomas NL, Helassa N J Cell Sci. 2022 Jan 15;135(2):jcs258796. doi: 10.1242/jcs.258796. Epub 2022 Jan , 18. PMID:34888671<ref>PMID:34888671</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6xxf" style="background-color:#fffaf0;"></div>

==See Also==
*[[Calmodulin 3D structures|Calmodulin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Antonyuk S]]
[[Category: Helassa N]]