View source for 1spy


==REGULATORY DOMAIN OF HUMAN CARDIAC TROPONIN C IN THE CALCIUM-FREE STATE, NMR, 40 STRUCTURES==
<StructureSection load='1spy' size='340' side='right'caption='[[1spy]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1spy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SPY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SPY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1spy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1spy OCA], [https://pdbe.org/1spy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1spy RCSB], [https://www.ebi.ac.uk/pdbsum/1spy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1spy ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TNNC1_HUMAN TNNC1_HUMAN] Defects in TNNC1 are the cause of cardiomyopathy dilated type 1Z (CMD1Z) [MIM:[https://omim.org/entry/611879 611879]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:15542288</ref>   Defects in TNNC1 are the cause of familial hypertrophic cardiomyopathy type 13 (CMH13) [MIM:[https://omim.org/entry/613243 613243]. A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.<ref>PMID:11385718</ref> <ref>PMID:16302972</ref> <ref>PMID:18572189</ref> <ref>PMID:19439414</ref> 
== Function ==
[https://www.uniprot.org/uniprot/TNNC1_HUMAN TNNC1_HUMAN] Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments.
== 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/sp/1spy_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=1spy ConSurf].
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== Publication Abstract from PubMed ==
While calcium binding to troponin C (TnC) triggers the contraction of both skeletal and cardiac muscle, there is clear evidence that different mechanisms may be involved. For example, activation of heart myofilaments occurs with binding to a single regulatory site on TnC, whereas activation of fast skeletal myofilaments occurs with binding to two regulatory sites. The physiological difference between activation of cardiac and skeletal myofilaments is not understood at the molecular level due to a lack of structural details for the response of cardiac TnC to calcium. We determined the solution structures of the apo and calcium-saturated regulatory domain of human cardiac TnC by using multinuclear, multidimensional nuclear magnetic resonance spectroscopy. The structure of apo human cardiac TnC is very similar to that of apo turkey skeletal TnC even though there are critical amino acid substitutions in site I. In contrast to the case with the skeletal protein, the calcium-induced conformational transition in the cardiac regulatory domain does not involve an "opening" of the regulatory domain, and the concomitant exposure of a substantial hydrophobic surface area. This result has important implications with regard to potential unique aspects of the interaction of cardiac TnC with cardiac troponin I and of modification of cardiac myofilament regulation by calcium-sensitizer drugs.

Calcium-induced structural transition in the regulatory domain of human cardiac troponin C.,Spyracopoulos L, Li MX, Sia SK, Gagne SM, Chandra M, Solaro RJ, Sykes BD Biochemistry. 1997 Oct 7;36(40):12138-46. PMID:9315850<ref>PMID:9315850</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Troponin 3D structures|Troponin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chandra M]]
[[Category: Gagne SM]]
[[Category: Li MX]]
[[Category: Sia SK]]
[[Category: Solaro RJ]]
[[Category: Spyracopoulos L]]
[[Category: Sykes BD]]