Roger Craig
Department of Cell Biology University of Massachusetts Medical School 55 Lake Avenue WORSTER MA 01655-0106
The molecular basis of thin filament linked regulation of contraction in striated and smooth muscles is not yet understood. We have been using electron microscopy combined with image processing and molecular fitting to define the molecular positions of tropomyosin and other regulatory proteins in thin filaments in the ON and OFF states. In striated muscle filaments, tropomyosin is found to block strong but not weak myosin binding sites on actin in the relaxed state. When activated by Ca2+, tropomyosin moves to expose most of the strong binding site, which could then activate myosin ATPase. Strong binding of myosin heads causes a further movement of tropomyosin, exposing the entire myosin binding site, which would further enhance ATPase, in a cooperative way. In smooth muscle thin filaments, containing caldesmon and tropomyosin, tropomyosin is in a position that exposes the myosin binding site in the OFF state. In the ON state, tropomyosin covers the myosin binding site. We conclude that caldesmon acts differently from troponin. Inhibition in the OFF state may be due to caldesmon itself covering the myosin binding site.