Predicting allosteric switches in myosins

The sequences of several members of the myosin family of molecular motors a re evaluated using ASP (Ambivalent Structure Predictor), a new computationa l method. ASP predicts structurally ambivalent sequence elements by analyzi ng the output from a secondary structure prediction algorithm. These ambiva lent sequence elements form secondary structures that are hypothesized to f unction as switches by undergoing conformational rearrangement. For chicken skeletal muscle myosin, 13 discrete structurally ambivalent sequence eleme nts are identified. All 13 are located in the heavy chain motor domain. Whe n these sequence elements are mapped into the myosin tertiary structure, th ey form two compact regions that connect the actin binding site to the aden osine 5'-triphosphate (ATP) site, and the ATP site to the fulcrum site for the force-producing bending of the motor domain. These regions, predicted b y the new algorithm to undergo conformational rearrangements, include the p ublished known and putative switches of the myosin motor domain, and they f orm plausible allosteric connections between the three main functional site s of myosin. The sequences of several other members of the myosin I and II families are also analyzed.