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2vaf

From Proteopedia

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Crystal structure of Human Cardiac Calsequestrin

Structural highlights

2vaf is a 1 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 2v0q. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.8Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CASQ2_HUMAN Defects in CASQ2 are the cause of catecholaminergic polymorphic ventricular tachycardia type 2 (CPVT2) [MIM: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.^[1] ^[2] ^[3] ^[4] ^[5]

Function

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.^[6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Mutations of conserved residues of human cardiac calsequestrin (hCSQ2), a high-capacity, low-affinity Ca2+-binding protein in the sarcoplasmic reticulum, have been associated with catecholamine-induced polymorphic ventricular tachycardia (CPVT). In order to understand the molecular mechanism and pathophysiological link between these CPVT-related missense mutations of hCSQ2 and the resulting arrhythmias, we generated three CPVT-causing mutants of hCSQ2 (R33Q, L167H, and D307H) and two non-pathological mutants (T66A and V76M) and investigated the effect of these mutations. In addition, we determined the crystal structure of the corresponding wild-type hCSQ2 to gain insight into the structural effects of those mutations. Our data show clearly that all three CPVT-related mutations lead to significant reduction in Ca2+-binding capacity in spite of the similarity of their secondary structures to that of the wild-type hCSQ2. Light-scattering experiments indicate that the Ca2+-dependent monomer-polymer transitions of the mutants are quite different, confirming that the linear polymerization behavior of CSQ is linked directly to its high-capacity Ca2+ binding. R33Q and D307H mutations result in a monomer that appears to be unable to form a properly oriented dimer. On the other hand, the L167H mutant has a disrupted hydrophobic core in domain II, resulting in high molecular aggregates, which cannot respond to Ca2+. Although one of the non-pathological mutants, T66A, shares characteristics with the wild-type, the other null mutant, V76M, shows significantly altered Ca2+-binding and polymerization behaviors, calling for careful reconsideration of its status.

Characterization of human cardiac calsequestrin and its deleterious mutants.,Kim E, Youn B, Kemper L, Campbell C, Milting H, Varsanyi M, Kang C J Mol Biol. 2007 Nov 2;373(4):1047-57. Epub 2007 Aug 29. PMID:17881003^[7]

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

References

↑ Kim E, Youn B, Kemper L, Campbell C, Milting H, Varsanyi M, Kang C. Characterization of human cardiac calsequestrin and its deleterious mutants. J Mol Biol. 2007 Nov 2;373(4):1047-57. Epub 2007 Aug 29. PMID:17881003 doi:10.1016/j.jmb.2007.08.055
↑ Lahat H, Pras E, Olender T, Avidan N, Ben-Asher E, Man O, Levy-Nissenbaum E, Khoury A, Lorber A, Goldman B, Lancet D, Eldar M. A missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in Bedouin families from Israel. Am J Hum Genet. 2001 Dec;69(6):1378-84. Epub 2001 Oct 25. PMID:11704930 doi:S0002-9297(07)61266-X
↑ Houle TD, Ram ML, Cala SE. Calsequestrin mutant D307H exhibits depressed binding to its protein targets and a depressed response to calcium. Cardiovasc Res. 2004 Nov 1;64(2):227-33. PMID:15485681 doi:S0008-6363(04)00394-3
↑ di Barletta MR, Viatchenko-Karpinski S, Nori A, Memmi M, Terentyev D, Turcato F, Valle G, Rizzi N, Napolitano C, Gyorke S, Volpe P, Priori SG. Clinical phenotype and functional characterization of CASQ2 mutations associated with catecholaminergic polymorphic ventricular tachycardia. Circulation. 2006 Sep 5;114(10):1012-9. Epub 2006 Aug 14. PMID:16908766 doi:CIRCULATIONAHA.106.623793
↑ Valle G, Galla D, Nori A, Priori SG, Gyorke S, de Filippis V, Volpe P. Catecholaminergic polymorphic ventricular tachycardia-related mutations R33Q and L167H alter calcium sensitivity of human cardiac calsequestrin. Biochem J. 2008 Jul 15;413(2):291-303. PMID:18399795 doi:BJ20080163
↑ Kim E, Youn B, Kemper L, Campbell C, Milting H, Varsanyi M, Kang C. Characterization of human cardiac calsequestrin and its deleterious mutants. J Mol Biol. 2007 Nov 2;373(4):1047-57. Epub 2007 Aug 29. PMID:17881003 doi:10.1016/j.jmb.2007.08.055
↑ Kim E, Youn B, Kemper L, Campbell C, Milting H, Varsanyi M, Kang C. Characterization of human cardiac calsequestrin and its deleterious mutants. J Mol Biol. 2007 Nov 2;373(4):1047-57. Epub 2007 Aug 29. PMID:17881003 doi:10.1016/j.jmb.2007.08.055

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2vaf"

@@ Line 3: / Line 3: @@
 <StructureSection load='2vaf' size='340' side='right'caption='[[2vaf]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2vaf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2v0q 2v0q]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VAF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VAF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2vaf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2v0q 2v0q]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VAF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VAF FirstGlance]. <br>
-</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=2vaf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vaf OCA], [https://pdbe.org/2vaf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vaf RCSB], [https://www.ebi.ac.uk/pdbsum/2vaf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vaf ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.8&#8491;</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=2vaf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vaf OCA], [https://pdbe.org/2vaf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vaf RCSB], [https://www.ebi.ac.uk/pdbsum/2vaf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vaf 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>
+[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>
+[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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 34: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Campbell, C]]
+[[Category: Campbell C]]
-[[Category: Kang, C]]
+[[Category: Kang C]]
-[[Category: Kemper, L]]
+[[Category: Kemper L]]
-[[Category: Kim, E]]
+[[Category: Kim E]]
-[[Category: Milting, H]]
+[[Category: Milting H]]
-[[Category: Varsanyi, M]]
+[[Category: Varsanyi M]]
-[[Category: Youn, B]]
+[[Category: Youn B]]
-[[Category: Calcium]]
-[[Category: Crystal structure human cardiac calsequestrin]]
-[[Category: Disease mutation]]
-[[Category: Glycoprotein]]
-[[Category: Metal binding protein]]
-[[Category: Metal-binding protein]]
-[[Category: Muscle protein]]
-[[Category: Polymorphism]]
-[[Category: Sarcoplasmic reticulum]]

2vaf

From Proteopedia

Current revision

Crystal structure of Human Cardiac Calsequestrin

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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