2vaf

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
m (Protected "2vaf" [edit=sysop:move=sysop])
Current revision (15:12, 13 December 2023) (edit) (undo)
 
(7 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:2vaf.png|left|200px]]
 
-
{{STRUCTURE_2vaf| PDB=2vaf | SCENE= }}
+
==Crystal structure of Human Cardiac Calsequestrin==
 +
<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/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='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>
 +
== 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>
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/va/2vaf_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vaf ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== 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.
-
===CRYSTAL STRUCTURE OF HUMAN CARDIAC CALSEQUESTRIN===
+
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<ref>PMID:17881003</ref>
-
{{ABSTRACT_PUBMED_17881003}}
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
 
+
</div>
-
==About this Structure==
+
<div class="pdbe-citations 2vaf" style="background-color:#fffaf0;"></div>
-
[[2vaf]] is a 1 chain structure with sequence from [http://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].
+
== References ==
-
 
+
<references/>
-
==Reference==
+
__TOC__
-
<ref group="xtra">PMID:017881003</ref><references group="xtra"/>
+
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Campbell, C.]]
+
[[Category: Large Structures]]
-
[[Category: Kang, C.]]
+
[[Category: Campbell C]]
-
[[Category: Kemper, L.]]
+
[[Category: Kang C]]
-
[[Category: Kim, E.]]
+
[[Category: Kemper L]]
-
[[Category: Milting, H.]]
+
[[Category: Kim E]]
-
[[Category: Varsanyi, M.]]
+
[[Category: Milting H]]
-
[[Category: Youn, B.]]
+
[[Category: Varsanyi M]]
-
[[Category: Crystal structure human cardiac calsequestrin]]
+
[[Category: Youn B]]
-
[[Category: Disease mutation]]
+
-
[[Category: Glycoprotein]]
+
-
[[Category: Metal-binding protein]]
+
-
[[Category: Muscle protein]]
+
-
[[Category: Sarcoplasmic reticulum]]
+

Current revision

Crystal structure of Human Cardiac Calsequestrin

PDB ID 2vaf

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

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