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==Central domain of cardiac myosin binding protein C==
==Central domain of cardiac myosin binding protein C==
<StructureSection load='1gxe' size='340' side='right'caption='[[1gxe]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
<StructureSection load='1gxe' size='340' side='right'caption='[[1gxe]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1gxe]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GXE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GXE FirstGlance]. <br>
<table><tr><td colspan='2'>[[1gxe]] 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=1GXE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GXE 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=1gxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gxe OCA], [https://pdbe.org/1gxe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gxe RCSB], [https://www.ebi.ac.uk/pdbsum/1gxe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gxe ProSAT]</span></td></tr>
</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=1gxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gxe OCA], [https://pdbe.org/1gxe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gxe RCSB], [https://www.ebi.ac.uk/pdbsum/1gxe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gxe ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[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>
== Function ==
[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.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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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=1gxe ConSurf].
</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=1gxe ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The large multidomain muscle protein myosin binding protein C (MyBP-C) has been implicated for some time in cardiac disease while until recently little was known about its structure and function. Here we present a detailed study of the central domain C5 of the cardiac isoform of MyBP-C. This domain is unusual in several aspects. Firstly it contains two sizeable insertions compared to the non-cardiac isoforms. The first insertion comprises the linker between domains cC4 and cC5 that is elongated by ten amino acid residues, the second insertion comprises an elongation of the CD-loop in the middle of the domain by approximately 30 amino acid residues. Secondly two point mutations linked to familial hypertrophic cardiomyopathy (FHC) have been identified in this domain. This work shows that the general fold of cC5 is in agreement with the IgI family of beta-sandwich structures. The long cardiac-specific linker between cC4 and cC5 is not a linker at all but an integral part of the fold of cC5, as evidenced by an unfolded mutant in which this segment was removed. The second insertion is shown to be unstructured, highly dynamic and mostly extended according to NMR relaxation measurements and analytical ultracentrifugation. The loss of several key interactions conserved in the CD-loop of the IgI fold is assumed to be responsible for the low stability of cC5 compared to other IgI domains from titin and MyBP-C itself. The low thermodynamic stability of cC5 is most evident in one of the two FHC-linked mutations, N755K (Asn115 in this construct) which is mainly unfolded with a small proportion of a native-like folded species. In contrast, the second FHC-linked mutation, R654H (Arg14 in this construct) is as well folded and stable as the wild-type. This residue is located in the extended beta-bulge at the N terminus of the protein, pointing towards the surface of the CFGA' beta-sheet. This position is in agreement with recent data pointing to a function of Arg654 in an intermolecular interaction with MyBP-C domain cC8.
Structure, stability and dynamics of the central domain of cardiac myosin binding protein C (MyBP-C): implications for multidomain assembly and causes for cardiomyopathy.,Idowu SM, Gautel M, Perkins SJ, Pfuhl M J Mol Biol. 2003 Jun 13;329(4):745-61. PMID:12787675<ref>PMID:12787675</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1gxe" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Pfuhl, M]]
[[Category: Pfuhl M]]
[[Category: Cytoskeleton]]
[[Category: Igi]]
[[Category: Immunoglobulin domain]]
[[Category: Muscle]]
[[Category: Thick filament]]
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