2mq3

From Proteopedia

(Difference between revisions)

Current revision

NMR structure of the c3 domain of human cardiac myosin binding protein-c with a hypertrophic cardiomyopathy-related mutation R502W.

Structural highlights

2mq3 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MYPC3_HUMAN Defects in MYBPC3 are the cause of familial hypertrophic cardiomyopathy type 4 (CMH4) [MIM: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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14] ^[15] ^[16] ^[17] ^[18] ^[19] ^[20]

Function

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.

Publication Abstract from PubMed

Human cardiac myosin binding protein C (cMyBP-C), a thick filament protein found within the sarcomere of cardiac muscle, regulates muscle contraction and is essential for proper muscle function. Hypertrophic cardiomyopathy (HCM), a genetic disease affecting 1 in 500 people, is the major cause of death in young athletes. It is caused by genetic mutations within sarcomeric proteins. Forty-two percent of the HCM-related mutations are found in cMyBP-C. Here we present the nuclear magnetic resonance-derived structural ensembles of the wild-type cMyBP-C C3 domain and its HCM-related R502W mutant. The C3 domain adopts an immunoglobulin-like fold, and mutation of the exposed Arg502 to a tryptophan does not perturb its structure, dynamics, or stability. However, the R502W mutation does alter the predicted electrostatic properties of the C3 domain. We hypothesize that this mutation, and other HCM-linked mutations found within the same domain, may directly disrupt the interaction of cMyBP-C with other sarcomeric proteins.

Structural Characterization of the C3 Domain of Cardiac Myosin Binding Protein C and Its Hypertrophic Cardiomyopathy-Related R502W Mutant.,Zhang XL, De S, McIntosh LP, Paetzel M Biochemistry. 2014 Aug 19;53(32):5332-42. doi: 10.1021/bi500784g. Epub 2014 Aug, 7. PMID:25058872^[21]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gautel M, Zuffardi O, Freiburg A, Labeit S. Phosphorylation switches specific for the cardiac isoform of myosin binding protein-C: a modulator of cardiac contraction? EMBO J. 1995 May 1;14(9):1952-60. PMID:7744002
↑ Carrier L, Bonne G, Bahrend E, Yu B, Richard P, Niel F, Hainque B, Cruaud C, Gary F, Labeit S, Bouhour JB, Dubourg O, Desnos M, Hagege AA, Trent RJ, Komajda M, Fiszman M, Schwartz K. Organization and sequence of human cardiac myosin binding protein C gene (MYBPC3) and identification of mutations predicted to produce truncated proteins in familial hypertrophic cardiomyopathy. Circ Res. 1997 Mar;80(3):427-34. PMID:9048664
↑ Niimura H, Bachinski LL, Sangwatanaroj S, Watkins H, Chudley AE, McKenna W, Kristinsson A, Roberts R, Sole M, Maron BJ, Seidman JG, Seidman CE. Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy. N Engl J Med. 1998 Apr 30;338(18):1248-57. PMID:9562578
↑ Yu B, French JA, Carrier L, Jeremy RW, McTaggart DR, Nicholson MR, Hambly B, Semsarian C, Richmond DR, Schwartz K, Trent RJ. Molecular pathology of familial hypertrophic cardiomyopathy caused by mutations in the cardiac myosin binding protein C gene. J Med Genet. 1998 Mar;35(3):205-10. PMID:9541104
↑ Moolman-Smook JC, Mayosi B, Brink P, Corfield VA. Identification of a new missense mutation in MyBP-C associated with hypertrophic cardiomyopathy. J Med Genet. 1998 Mar;35(3):253-4. PMID:9541115
↑ Maron BJ, Niimura H, Casey SA, Soper MK, Wright GB, Seidman JG, Seidman CE. Development of left ventricular hypertrophy in adults in hypertrophic cardiomyopathy caused by cardiac myosin-binding protein C gene mutations. J Am Coll Cardiol. 2001 Aug;38(2):315-21. PMID:11499718
↑ Erdmann J, Raible J, Maki-Abadi J, Hummel M, Hammann J, Wollnik B, Frantz E, Fleck E, Hetzer R, Regitz-Zagrosek V. Spectrum of clinical phenotypes and gene variants in cardiac myosin-binding protein C mutation carriers with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2001 Aug;38(2):322-30. PMID:11499719
↑ Daehmlow S, Erdmann J, Knueppel T, Gille C, Froemmel C, Hummel M, Hetzer R, Regitz-Zagrosek V. Novel mutations in sarcomeric protein genes in dilated cardiomyopathy. Biochem Biophys Res Commun. 2002 Oct 18;298(1):116-20. PMID:12379228
↑ Niimura H, Patton KK, McKenna WJ, Soults J, Maron BJ, Seidman JG, Seidman CE. Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly. Circulation. 2002 Jan 29;105(4):446-51. PMID:11815426
↑ Nanni L, Pieroni M, Chimenti C, Simionati B, Zimbello R, Maseri A, Frustaci A, Lanfranchi G. Hypertrophic cardiomyopathy: two homozygous cases with "typical" hypertrophic cardiomyopathy and three new mutations in cases with progression to dilated cardiomyopathy. Biochem Biophys Res Commun. 2003 Sep 19;309(2):391-8. PMID:12951062
↑ Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, Benaiche A, Isnard R, Dubourg O, Burban M, Gueffet JP, Millaire A, Desnos M, Schwartz K, Hainque B, Komajda M. Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation. 2003 May 6;107(17):2227-32. Epub 2003 Apr 21. PMID:12707239 doi:10.1161/01.CIR.0000066323.15244.54
↑ Erdmann J, Daehmlow S, Wischke S, Senyuva M, Werner U, Raible J, Tanis N, Dyachenko S, Hummel M, Hetzer R, Regitz-Zagrosek V. Mutation spectrum in a large cohort of unrelated consecutive patients with hypertrophic cardiomyopathy. Clin Genet. 2003 Oct;64(4):339-49. PMID:12974739
↑ Alders M, Jongbloed R, Deelen W, van den Wijngaard A, Doevendans P, Ten Cate F, Regitz-Zagrosek V, Vosberg HP, van Langen I, Wilde A, Dooijes D, Mannens M. The 2373insG mutation in the MYBPC3 gene is a founder mutation, which accounts for nearly one-fourth of the HCM cases in the Netherlands. Eur Heart J. 2003 Oct;24(20):1848-53. PMID:14563344
↑ Konno T, Shimizu M, Ino H, Matsuyama T, Yamaguchi M, Terai H, Hayashi K, Mabuchi T, Kiyama M, Sakata K, Hayashi T, Inoue M, Kaneda T, Mabuchi H. A novel missense mutation in the myosin binding protein-C gene is responsible for hypertrophic cardiomyopathy with left ventricular dysfunction and dilation in elderly patients. J Am Coll Cardiol. 2003 Mar 5;41(5):781-6. PMID:12628722
↑ Morner S, Richard P, Kazzam E, Hellman U, Hainque B, Schwartz K, Waldenstrom A. Identification of the genotypes causing hypertrophic cardiomyopathy in northern Sweden. J Mol Cell Cardiol. 2003 Jul;35(7):841-9. PMID:12818575
↑ Andersen PS, Havndrup O, Bundgaard H, Larsen LA, Vuust J, Pedersen AK, Kjeldsen K, Christiansen M. Genetic and phenotypic characterization of mutations in myosin-binding protein C (MYBPC3) in 81 families with familial hypertrophic cardiomyopathy: total or partial haploinsufficiency. Eur J Hum Genet. 2004 Aug;12(8):673-7. PMID:15114369 doi:10.1038/sj.ejhg.5201190
↑ Van Driest SL, Vasile VC, Ommen SR, Will ML, Tajik AJ, Gersh BJ, Ackerman MJ. Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2004 Nov 2;44(9):1903-10. PMID:15519027 doi:S0735-1097(04)01614-6
↑ Song L, Zou Y, Wang J, Wang Z, Zhen Y, Lou K, Zhang Q, Wang X, Wang H, Li J, Hui R. Mutations profile in Chinese patients with hypertrophic cardiomyopathy. Clin Chim Acta. 2005 Jan;351(1-2):209-16. PMID:15563892 doi:10.1016/j.cccn.2004.09.016
↑ Ingles J, Doolan A, Chiu C, Seidman J, Seidman C, Semsarian C. Compound and double mutations in patients with hypertrophic cardiomyopathy: implications for genetic testing and counselling. J Med Genet. 2005 Oct;42(10):e59. PMID:16199542 doi:10.1136/jmg.2005.033886
↑ Morita H, Rehm HL, Menesses A, McDonough B, Roberts AE, Kucherlapati R, Towbin JA, Seidman JG, Seidman CE. Shared genetic causes of cardiac hypertrophy in children and adults. N Engl J Med. 2008 May 1;358(18):1899-908. doi: 10.1056/NEJMoa075463. Epub 2008, Apr 9. PMID:18403758 doi:10.1056/NEJMoa075463
↑ Zhang XL, De S, McIntosh LP, Paetzel M. Structural Characterization of the C3 Domain of Cardiac Myosin Binding Protein C and Its Hypertrophic Cardiomyopathy-Related R502W Mutant. Biochemistry. 2014 Aug 19;53(32):5332-42. doi: 10.1021/bi500784g. Epub 2014 Aug, 7. PMID:25058872 doi:http://dx.doi.org/10.1021/bi500784g

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2mq3"

@@ Line 1: / Line 1: @@
 ==NMR structure of the c3 domain of human cardiac myosin binding protein-c with a hypertrophic cardiomyopathy-related mutation R502W.==
-<StructureSection load='2mq3' size='340' side='right'caption='[[2mq3]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
+<StructureSection load='2mq3' size='340' side='right'caption='[[2mq3]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2mq3]] 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=2MQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MQ3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2mq3]] 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=2MQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MQ3 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2mq0|2mq0]]</div></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MYBPC3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2mq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mq3 OCA], [https://pdbe.org/2mq3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mq3 RCSB], [https://www.ebi.ac.uk/pdbsum/2mq3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mq3 ProSAT]</span></td></tr>
 </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>
+[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.
+[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.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: De, S]]
+[[Category: De S]]
-[[Category: Mcintosh, L P]]
+[[Category: Mcintosh LP]]
-[[Category: Paetzel, M]]
+[[Category: Paetzel M]]
-[[Category: Zhang, X]]
+[[Category: Zhang X]]
-[[Category: C3 domain]]
-[[Category: Cardiac myosin binding protein c]]
-[[Category: Contractile protein]]
-[[Category: Hypertrophic cardiomyopathy]]
-[[Category: Ig-like]]

2mq3

From Proteopedia

Current revision

NMR structure of the c3 domain of human cardiac myosin binding protein-c with a hypertrophic cardiomyopathy-related mutation R502W.

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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