6jv2

From Proteopedia

(Difference between revisions)

Revision as of 15:57, 28 August 2019

Structure of RyR2 (P/L-Ca2+/Ca2+-CaM dataset)

Structural highlights

6jv2 is a 8 chain structure with sequence from Human and Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	CALM1, CALM, CAM, CAM1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CALM1_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of LQT14.

Function

[CALM1_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).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

The high-conductance intracellular calcium (Ca(2+)) channel RyR2 is essential for the coupling of excitation and contraction in cardiac muscle. Among various modulators, calmodulin (CaM) regulates RyR2 in a Ca(2+)-dependent manner. Here we reveal the regulatory mechanism by which porcine RyR2 is modulated by human CaM through the structural determination of RyR2 under eight conditions. Apo-CaM and Ca(2+)-CaM bind to distinct but overlapping sites in an elongated cleft formed by the handle, helical and central domains. The shift in CaM-binding sites on RyR2 is controlled by Ca(2+) binding to CaM, rather than to RyR2. Ca(2+)-CaM induces rotations and intradomain shifts of individual central domains, resulting in pore closure of the PCB95 and Ca(2+)-activated channel. By contrast, the pore of the ATP, caffeine and Ca(2+)-activated channel remains open in the presence of Ca(2+)-CaM, which suggests that Ca(2+)-CaM is one of the many competing modulators of RyR2 gating.

Modulation of cardiac ryanodine receptor 2 by calmodulin.,Gong D, Chi X, Wei J, Zhou G, Huang G, Zhang L, Wang R, Lei J, Chen SRW, Yan N Nature. 2019 Jul 5. pii: 10.1038/s41586-019-1377-y. doi:, 10.1038/s41586-019-1377-y. PMID:31278385^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Tsang WY, Spektor A, Luciano DJ, Indjeian VB, Chen Z, Salisbury JL, Sanchez I, Dynlacht BD. CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability. Mol Biol Cell. 2006 Aug;17(8):3423-34. Epub 2006 Jun 7. PMID:16760425 doi:10.1091/mbc.E06-04-0371
↑ Reichow SL, Clemens DM, Freites JA, Nemeth-Cahalan KL, Heyden M, Tobias DJ, Hall JE, Gonen T. Allosteric mechanism of water-channel gating by Ca-calmodulin. Nat Struct Mol Biol. 2013 Jul 28. doi: 10.1038/nsmb.2630. PMID:23893133 doi:10.1038/nsmb.2630
↑ Boczek NJ, Gomez-Hurtado N, Ye D, Calvert ML, Tester DJ, Kryshtal D, Hwang HS, Johnson CN, Chazin WJ, Loporcaro CG, Shah M, Papez AL, Lau YR, Kanter R, Knollmann BC, Ackerman MJ. Spectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded Calmodulin Variants in Long QT Syndrome and Functional Characterization of a Novel Long QT Syndrome-Associated Calmodulin Missense Variant, E141G. Circ Cardiovasc Genet. 2016 Apr;9(2):136-146. doi:, 10.1161/CIRCGENETICS.115.001323. Epub 2016 Mar 11. PMID:26969752 doi:http://dx.doi.org/10.1161/CIRCGENETICS.115.001323
↑ Yu CC, Ko JS, Ai T, Tsai WC, Chen Z, Rubart M, Vatta M, Everett TH 4th, George AL Jr, Chen PS. Arrhythmogenic calmodulin mutations impede activation of small-conductance calcium-activated potassium current. Heart Rhythm. 2016 Aug;13(8):1716-23. doi: 10.1016/j.hrthm.2016.05.009. Epub 2016, May 7. PMID:27165696 doi:http://dx.doi.org/10.1016/j.hrthm.2016.05.009
↑ Gong D, Chi X, Wei J, Zhou G, Huang G, Zhang L, Wang R, Lei J, Chen SRW, Yan N. Modulation of cardiac ryanodine receptor 2 by calmodulin. Nature. 2019 Jul 5. pii: 10.1038/s41586-019-1377-y. doi:, 10.1038/s41586-019-1377-y. PMID:31278385 doi:http://dx.doi.org/10.1038/s41586-019-1377-y

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6jv2"

@@ Line 3: / Line 3: @@
 <StructureSection load='6jv2' size='340' side='right'caption='[[6jv2]], [[Resolution|resolution]] 4.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6jv2]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JV2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JV2 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6jv2]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JV2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JV2 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CALM1, CALM, CAM, CAM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <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=6jv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jv2 OCA], [http://pdbe.org/6jv2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jv2 RCSB], [http://www.ebi.ac.uk/pdbsum/6jv2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jv2 ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/CALM1_HUMAN CALM1_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4.  The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of LQT14.
+== Function ==
+[[http://www.uniprot.org/uniprot/CALM1_HUMAN CALM1_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:23893133</ref> <ref>PMID:26969752</ref> <ref>PMID:27165696</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Sus scrofa]]

6jv2

From Proteopedia

Revision as of 15:57, 28 August 2019

Structure of RyR2 (P/L-Ca2+/Ca2+-CaM dataset)

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox