“The mechanism of ATPase inhibition in smooth muscle myosin”
Kenneth Taylor – Institute of Molecular Biophysics, Florida State University
The actin activated ATPase activity of smooth muscle and non-muscle myosin is controlled by phosphorylation of the regulatory light chain. RLC phosphorylation affects not only ATPase activity but also solubility. Nonphosphorylated myosin is soluble at physiological ionic strength in the presence of ATP whereas phosphorylated myosin forms filaments. Inhibition also requires that both heads be present; single headed fragments and S1 are not inhibited. Structural studies of 2-D arrays of both the soluble 2-headed fragment of myosin, heavy meromyosin (HMM) and whole myosin has shown that an asymmetric head-head interaction forms the basis of ATPase inhibition. However, they don’t explain the changes in solubility. To explore the solubility and other aspects of the conformational change to the inhibited state, we have applied normal mode analysis starting from hypothetical starting structures using the atomic model of smooth muscle HMM in the ephosphorylated state obtained by Wendt et al. as the target structure. The results suggest that the solubility changes are due to distortion of the coiled-coil of the rod domain. In addition, the results suggest that two heptads of the coiled-coil rod domain are not coiled.