2avg

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{{Seed}}
 
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[[Image:2avg.png|left|200px]]
 
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==NMR structure of cC1 domain from Human Cardiac Myosin Binding Protein C==
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The line below this paragraph, containing "STRUCTURE_2avg", creates the "Structure Box" on the page.
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<StructureSection load='2avg' size='340' side='right'caption='[[2avg]]' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2avg]] 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=2AVG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AVG FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2avg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2avg OCA], [https://pdbe.org/2avg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2avg RCSB], [https://www.ebi.ac.uk/pdbsum/2avg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2avg ProSAT]</span></td></tr>
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{{STRUCTURE_2avg| PDB=2avg | SCENE= }}
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/MYPC3_HUMAN MYPC3_HUMAN] Defects in MYBPC3 are the cause of familial hypertrophic cardiomyopathy type 4 (CMH4) [MIM:[https://omim.org/entry/115197 115197]. Familial hypertrophic cardiomyopathy is 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:7744002</ref> <ref>PMID:9048664</ref> <ref>PMID:9562578</ref> <ref>PMID:9541104</ref> <ref>PMID:9541115</ref> <ref>PMID:11499718</ref> <ref>PMID:11499719</ref> <ref>PMID:12379228</ref> <ref>PMID:11815426</ref> <ref>PMID:12951062</ref> <ref>PMID:12707239</ref> <ref>PMID:12974739</ref> <ref>PMID:14563344</ref> <ref>PMID:12628722</ref> <ref>PMID:12818575</ref> <ref>PMID:15114369</ref> <ref>PMID:15519027</ref> <ref>PMID:15563892</ref> <ref>PMID:16199542</ref> <ref>PMID:18403758</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/MYPC3_HUMAN MYPC3_HUMAN] Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. It may modulate muscle contraction or may play a more structural role.
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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/av/2avg_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=2avg 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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Myosin binding protein C (MyBP-C) is a thick filament protein involved in the regulation of muscle contraction. Mutations in the gene for MyBP-C are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. It is assumed that the function of MyBP-C is to act as a tether that fixes the S1 heads in a resting position and that phosphorylation releases the S1 heads into an active state. Here, we report the structure and binding properties of domain C1. Using a combination of site-directed mutagenesis and NMR interaction experiments, we identified the binding site of domain C1 in the immediate vicinity of the S1-S2 hinge, very close to the light chains. In addition, we identified a zinc binding site on domain C1 in close proximity to the S2 binding site. Its zinc binding affinity (K(d) of approximately 10-20 microM) might not be sufficient for a physiological effect. However, the familial hypertrophic cardiomyopathy-related mutation of one of the zinc ligands, glutamine 210 to histidine, will significantly increase the binding affinity, suggesting that this mutation may affect S2 binding. The close proximity of the C1 binding site to the hinge, the light chains and the S1 heads also provides an explanation for recent observations that (a) shorter fragments of MyBP-C unable to act as a tether still have an effect on the actomyosin ATPase and (b) as to why the myosin head positions in phosphorylated wild-type mice and MyBP-C knockout mice are so different: Domain C1 bound to the S1-S2 hinge is able to manipulate S1 head positions, thus influencing force generation without tether. The potentially extensive extra interactions of C1 are expected to keep it in place, while phosphorylation dislodges the C1-C2 linker and domain C2. As a result, the myosin heads would always be attached to a tether that has phosphorylation-dependent length regulation.
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===NMR structure of cC1 domain from Human Cardiac Myosin Binding Protein C===
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Myosin binding protein C positioned to play a key role in regulation of muscle contraction: structure and interactions of domain C1.,Ababou A, Rostkova E, Mistry S, Le Masurier C, Gautel M, Pfuhl M J Mol Biol. 2008 Dec 19;384(3):615-30. Epub 2008 Oct 7. PMID:18926831<ref>PMID:18926831</ref>
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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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The line below this paragraph, {{ABSTRACT_PUBMED_18926831}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 2avg" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 18926831 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_18926831}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2AVG is a 1 chain structure of 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=2AVG OCA].
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==Reference==
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<ref group="xtra">PMID:18926831</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Ababou, A.]]
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[[Category: Large Structures]]
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[[Category: Gautel, M.]]
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[[Category: Ababou A]]
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[[Category: Pfuhl, M.]]
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[[Category: Gautel M]]
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[[Category: Human cardiac mybp-c]]
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[[Category: Pfuhl M]]
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[[Category: Structural protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 10 21:59:48 2009''
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Current revision

NMR structure of cC1 domain from Human Cardiac Myosin Binding Protein C

PDB ID 2avg

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