Key Points
- To determine the spatial organisation and structural role of myosin binding protein C (MyBP-C) across cardiac and skeletal muscle, using MyBP-C knockout models for comparison.
- Analysed electron micrographs of well-preserved cardiac and skeletal muscle using a novel averaging technique to measure axial density across A-bands.
- Employed antibody labelling to localize MyBP-C within the accessory protein stripes of the A-band.
- Examined thick filament periodicities and extra meridional reflections in normal versus MyBP-C-deficient mouse cardiac muscle using X-ray diffraction patterns.
- Cardiac and skeletal A-bands showed nearly identical lengths (1.58 ± 0.01 µm) with 11 prominent accessory protein stripes spaced at 43-nm intervals in each half of the A-band.
- Antibody labelling localized MyBP-C specifically to the distal nine stripes, which were markedly suppressed in MyBP-C knockout mouse hearts.
- Forbidden meridional reflections at 43-nm orders in X-ray diffraction were weak or absent in knockout tissue, attributing these reflections directly to MyBP-C or its perturbation of myosin heads.
Structured PICO
PPopulationNormal striated muscle (cardiac and skeletal) and MyBP-C-deficient (knockout) mouse hearts
IInterventionMyBP-C knockout
CComparatorNormal cardiac and skeletal muscle
OOutcomeDistribution of MyBP-C in the A-bands and axial density distributionsurrogate
The study demonstrates that MyBP-C is located in the distal nine stripes of the A-band and is responsible for the extra meridional reflections in X-ray diffraction patterns of muscle.