2v6h

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2v6h, resolution 1.55Å ()
Related: 1gxe, 1pd6
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

CRYSTAL STRUCTURE OF THE C1 DOMAIN OF CARDIAC MYOSIN BINDING PROTEIN-C

Publication Abstract from PubMed

C-protein is a major component of skeletal and cardiac muscle thick filaments. Mutations in the gene encoding cardiac C-protein [cardiac myosin binding protein-C (cMyBP-C)] are one of the principal causes of hypertrophic cardiomyopathy. cMyBP-C is a string of globular domains including eight immunoglobulin-like and three fibronectin-like domains termed C0-C10. It binds to myosin and titin, and probably to actin, and may have both a structural and a regulatory role in muscle function. To help to understand the pathology of the known mutations, we have solved the structure of the immunoglobulin-like C1 domain of MyBP-C by X-ray crystallography to a resolution of 1.55 A. Mutations associated with hypertrophic cardiomyopathy are clustered at one end towards the C-terminus, close to the important C1C2 linker, where they alter the structural integrity of this region and its interactions.

Crystal structure of the C1 domain of cardiac myosin binding protein-C: implications for hypertrophic cardiomyopathy., Govada L, Carpenter L, da Fonseca PC, Helliwell JR, Rizkallah P, Flashman E, Chayen NE, Redwood C, Squire JM, J Mol Biol. 2008 Apr 25;378(2):387-97. Epub 2008 Mar 4. PMID:18374358

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

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.

About this Structure

2v6h is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • Govada L, Carpenter L, da Fonseca PC, Helliwell JR, Rizkallah P, Flashman E, Chayen NE, Redwood C, Squire JM. Crystal structure of the C1 domain of cardiac myosin binding protein-C: implications for hypertrophic cardiomyopathy. J Mol Biol. 2008 Apr 25;378(2):387-97. Epub 2008 Mar 4. PMID:18374358 doi:10.1016/j.jmb.2008.02.044
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  13. 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
  14. 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
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  19. 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
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