Understanding the Organisation and Role of Myosin Binding Protein C in Normal Striated Muscle by Comparison with MyBP-C Knockout Cardiac Muscle

Pradeep K. Luther, Pauline M. Bennett, Carlo Knupp, Roger Craig, Raúl Padrón, Samantha P. Harris, Jitendrakumar Patel, Richard L. Moss

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Myosin binding protein C (MyBP-C) is a component of the thick filament of striated muscle. The importance of this protein is revealed by recent evidence that mutations in the cardiac gene are a major cause of familial hypertrophic cardiomyopathy. Here we investigate the distribution of MyBP-C in the A-bands of cardiac and skeletal muscles and compare this to the A-band structure in cardiac muscle of MyBP-C-deficient mice. We have used a novel averaging technique to obtain the axial density distribution of A-bands in electron micrographs of well-preserved specimens. We show that cardiac and skeletal A-bands are very similar, with a length of 1.58 ± 0.01 μm. In normal cardiac and skeletal muscle, the distributions are very similar, showing clearly the series of 11 prominent accessory protein stripes in each half of the A-band spaced axially at 43-nm intervals and starting at the edge of the bare zone. We show by antibody labelling that in cardiac muscle the distal nine stripes are the location of MyBP-C. These stripes are considerably suppressed in the knockout mouse hearts as expected. Myosin heads on the surface of the thick filament in relaxed muscle are thought to be arranged in a three-stranded quasi-helix with a mean 14.3-nm axial cross bridge spacing and a 43 nm helix repeat. Extra "forbidden" meridional reflections, at orders of 43 nm, in X-ray diffraction patterns of muscle have been interpreted as due to an axial perturbation of some levels of myosin heads. However, in the MyBP-C-deficient hearts these extra meridional reflections are weak or absent, suggesting that they are due to MyBP-C itself or to MyBP-C in combination with a head perturbation brought about by the presence of MyBP-C.

Original languageEnglish (US)
Pages (from-to)60-72
Number of pages13
JournalJournal of Molecular Biology
Volume384
Issue number1
DOIs
StatePublished - Dec 5 2008

Fingerprint

Striated Muscle
Myocardium
Myosins
Skeletal Muscle
Familial Hypertrophic Cardiomyopathy
Cardiac Myosins
Muscles
Knockout Mice
X-Ray Diffraction
myosin-binding protein C
Proteins
Head
Electrons
Mutation
Antibodies
Genes

Keywords

  • cardiac muscle
  • cryosections
  • electron microscopy
  • myosin-binding protein C

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Understanding the Organisation and Role of Myosin Binding Protein C in Normal Striated Muscle by Comparison with MyBP-C Knockout Cardiac Muscle. / Luther, Pradeep K.; Bennett, Pauline M.; Knupp, Carlo; Craig, Roger; Padrón, Raúl; Harris, Samantha P.; Patel, Jitendrakumar; Moss, Richard L.

In: Journal of Molecular Biology, Vol. 384, No. 1, 05.12.2008, p. 60-72.

Research output: Contribution to journalArticle

Luther, Pradeep K. ; Bennett, Pauline M. ; Knupp, Carlo ; Craig, Roger ; Padrón, Raúl ; Harris, Samantha P. ; Patel, Jitendrakumar ; Moss, Richard L. / Understanding the Organisation and Role of Myosin Binding Protein C in Normal Striated Muscle by Comparison with MyBP-C Knockout Cardiac Muscle. In: Journal of Molecular Biology. 2008 ; Vol. 384, No. 1. pp. 60-72.
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AB - Myosin binding protein C (MyBP-C) is a component of the thick filament of striated muscle. The importance of this protein is revealed by recent evidence that mutations in the cardiac gene are a major cause of familial hypertrophic cardiomyopathy. Here we investigate the distribution of MyBP-C in the A-bands of cardiac and skeletal muscles and compare this to the A-band structure in cardiac muscle of MyBP-C-deficient mice. We have used a novel averaging technique to obtain the axial density distribution of A-bands in electron micrographs of well-preserved specimens. We show that cardiac and skeletal A-bands are very similar, with a length of 1.58 ± 0.01 μm. In normal cardiac and skeletal muscle, the distributions are very similar, showing clearly the series of 11 prominent accessory protein stripes in each half of the A-band spaced axially at 43-nm intervals and starting at the edge of the bare zone. We show by antibody labelling that in cardiac muscle the distal nine stripes are the location of MyBP-C. These stripes are considerably suppressed in the knockout mouse hearts as expected. Myosin heads on the surface of the thick filament in relaxed muscle are thought to be arranged in a three-stranded quasi-helix with a mean 14.3-nm axial cross bridge spacing and a 43 nm helix repeat. Extra "forbidden" meridional reflections, at orders of 43 nm, in X-ray diffraction patterns of muscle have been interpreted as due to an axial perturbation of some levels of myosin heads. However, in the MyBP-C-deficient hearts these extra meridional reflections are weak or absent, suggesting that they are due to MyBP-C itself or to MyBP-C in combination with a head perturbation brought about by the presence of MyBP-C.

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