2jxl

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[[Image:2jxl.png|left|200px]]
 
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{{STRUCTURE_2jxl| PDB=2jxl | SCENE= }}
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==Solution structure of cardiac N-domain troponin C mutant F77W-V82A==
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<StructureSection load='2jxl' size='340' side='right'caption='[[2jxl]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2jxl]] 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=2JXL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JXL FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2jxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jxl OCA], [https://pdbe.org/2jxl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jxl RCSB], [https://www.ebi.ac.uk/pdbsum/2jxl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jxl ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jx/2jxl_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2jxl ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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In situ fluorescence/NMR spectroscopic approaches have been used to elucidate the structure, mobility, and domain orientations of troponin C in striated muscle. This led us to consider complementary approaches such as solid-state NMR spectroscopy. The biophysical properties of tryptophan and Trp-analogues, such as fluorotryptophan or hydroxytryptophan, are often exploited to probe protein structure and dynamics using solid-state NMR or fluorescence spectroscopy. We have characterized Phe-to-Trp mutants in the 'structural' C-domain of cardiac troponin C, designed to immobilize the indole ring in the hydrophobic core of the domain. The mutations and their fluorinated analogues (F104W, F104(5fW), F153W, and F153(5fW)) were shown not to perturb the structural properties of the protein. In this paper, we characterize the mutations F77W and F77W-V82A in the 'regulatory' N-domain of cardiac troponin C. We used NMR to determine the structure and dynamics of the mutant F77W-V82A-cNTnC, which shows a unique orientation of the indole ring. We observed a decrease in calcium binding affinity and a weaker affinity for the switch region of TnI for both mutants. We present force recovery measurements for all of the N- and C-domain mutants reconstituted into skeletal muscle fibers. The F77W mutation leads to a reduction of the in situ force recovery, whereas the C-domain mutants have the same activity as the wild type. These results suggest that the perturbations of the N-domain caused by the Trp mutation disturb the interaction between TnC and TnI, which in turn diminishes the activity in fibers, providing a clear example of the correlation between in vitro protein structures, their interactions, and the resulting in situ physiological activity.
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===Solution structure of cardiac N-domain troponin C mutant F77W-V82A===
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Tryptophan mutants of cardiac troponin C: 3D structure, troponin I affinity, and in situ activity.,Julien O, Sun YB, Wang X, Lindhout DA, Thiessen A, Irving M, Sykes BD Biochemistry. 2008 Jan 15;47(2):597-606. Epub 2007 Dec 20. PMID:18092822<ref>PMID:18092822</ref>
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{{ABSTRACT_PUBMED_18092822}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 2jxl" style="background-color:#fffaf0;"></div>
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[[2jxl]] is a 1 chain structure of [[Troponin]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JXL OCA].
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==See Also==
==See Also==
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*[[Troponin|Troponin]]
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*[[Troponin 3D structures|Troponin 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:018092822</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Irving, M.]]
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[[Category: Large Structures]]
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[[Category: Julien, O.]]
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[[Category: Irving M]]
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[[Category: Lindhout, D A.]]
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[[Category: Julien O]]
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[[Category: Sun, Y.]]
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[[Category: Lindhout DA]]
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[[Category: Sykes, B D.]]
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[[Category: Sun Y]]
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[[Category: Thiessen, A.]]
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[[Category: Sykes BD]]
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[[Category: Wang, X.]]
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[[Category: Thiessen A]]
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[[Category: Cntnc]]
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[[Category: Wang X]]
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[[Category: F77w]]
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[[Category: Muscle protein]]
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[[Category: Structural protein]]
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[[Category: Troponin c]]
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[[Category: Tryptophan]]
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Current revision

Solution structure of cardiac N-domain troponin C mutant F77W-V82A

PDB ID 2jxl

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