STRUCTURAL BASIS OF MYOSIN MOTILITY. I. Rayment, A.J. Fisher, C.A. Smith, A. Gulick, R. Smith, H.M. Holden and K. Sutoh , Institute for Enzyme Research and Department of Biochemistry, University of Wisconsin, Madison WI 53705, and Department of Pure and Applied Sciences, University of Tokyo, Komba, Tokyo 153 Japan

The mechanism by which chemical energy is transduced into directed movement in muscle and myosin-based motility is a fundamental question in biology. Recently considerable progress has been made towards establishing the molecular basis of the sliding filament model that was proposed over 40 years ago through the determination of the three-dimensional structures of actin (Kabsch et al., 1990, Nature, 347, 37-44) and myosin subfragment-1 (Rayment et al., 1993, Science, 261, 50-58). These have provided a structural framework for a molecular hypothesis for muscle contraction (Rayment et al., 1993, Science, 261, 58-65). Even so many questions remain concerning the structural transitions that underlie the conversion of chemical energy into directed movement. In an effort to understand how ATP hydrolysis is coupled to movement we have determined the structure of a genetically truncated myosin head in the presence of more than seven substrate analogs including MgADP, MgPPi, MgATP[[gamma]]S, MgAMPPNP, MgADP^.BeF_x, MgADP^.AlF⁴, MgADP^.VO⁴ and several non-ATP derivatives that support tension. These complexes suggest a structural mechanism for ATP hydrolysis and new model for the conformational changes that underlie myosin-based motility.