Practice question

Skeletal muscle thin filaments extend from Z disc to near M line, length precisely regulated 1.0 micrometer in cardiac, 1.1 to 1.3 in skeletal for optimal overlap with thick filaments for force generation. Nebulin, 600 to 900 kilodalton protein encoded by NEB gene, composed of 185 tandem nebulin repeats of 35 amino acids each predicted to contact single actin monomer plus C terminal SH3 domain anchoring at Z disc via interactions with CapZ, titin Z repeats and desmin intermediate filaments. By spanning entire thin filament, nebulin acts as molecular ruler templating polymerization length during myofibrillogenesis and stabilizing filament against lateral sliding and cofilin mediated severing. Structural studies show repeats align along actin helical groove stabilizing interaction with tropomyosin troponin. Human null mutations cause nemaline myopathy with variable thin filament length and weakness. CapZ caps barbed plus end, tropomodulin caps pointed minus end, gelsolin severs, but lateral stabilization along whole shaft best described by nebulin ruler function important for muscle structure.