title: Understanding the organisation and role of myosin binding protein C in normal striated muscle by comparison with MyBP-C knockout cardiac muscle.
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 mum. 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.
authors.affiliation: Molecular Medicine Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London SW72AZ, UK. p.luther@imperial.ac.uk
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Luther
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Bennett
authors.forename: Carlo
authors.initials: C
authors.lastname: Knupp
authors.forename: Roger
authors.initials: R
authors.lastname: Craig
authors.forename: Raúl
authors.initials: R
authors.lastname: Padrón
authors.forename: Samantha P
authors.initials: SP
authors.lastname: Harris
authors.forename: Jitendrakumar
authors.initials: J
authors.lastname: Patel
authors.forename: Richard L
authors.initials: RL
authors.lastname: Moss
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D005583:Fourier Analysis; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000648:ultrastructure; D017434:Protein Structure, Tertiary; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C