A myosin II mutation uncouples ATPase activity from motility and shortens step size

It is thought that Switch II of myosin, kinesin and G proteins has an impor tant function in relating nucleotide state to protein conformation, Here we examine a myosin mutant containing an S456L substitution in the Switch II region. In this protein, mechanical activity is uncoupled from the chemical energy of ATP hydrolysis so that its gliding velocity on actin filaments i s only one-tenth of that of the wild type. The mutant spends longer in the strongly bound state and exhibits a shorter step size, which together accou nt for the reduction in in vitro velocity. This is the first single point m utation in myosin that has been found to affect step size.