Predicting allosteric switches in myosins.
The sequences of several members of the myosin family of molecular motors are evaluated using ASP (Ambivalent Structure Predictor), a new computational method. ASP predicts structurally ambivalent sequence elements by analyzing the output from a secondary structure prediction algorithm. These ambivalent sequence elements form secondary structures that are hypothesized to function as switches by undergoing conformational rearrangement. For chicken skeletal muscle myosin, 13 discrete structurally ambivalent sequence elements are identified. All 13 are located in the heavy chain motor domain. When these sequence elements are mapped into the myosin tertiary structure, they form two compact regions that connect the actin binding site to the adenosine 5'-triphosphate (ATP) site, and the ATP site to the fulcrum site for the force-producing bending of the motor domain. These regions, predicted by the new algorithm to undergo conformational rearrangements, include the published known and putative switches of the myosin motor domain, and they form plausible allosteric connections between the three main functional sites of myosin. The sequences of several other members of the myosin I and II families are also analyzed.
Kirshenbaum
K
K
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143, USA.
Young
M
M
Highsmith
S
S
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D019295:Computational Biology / Q000379:methods*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000737:chemistry; D018995:Myosin Heavy Chains / Q000737:chemistry; D009218:Myosins / Q000737:chemistry* / Q000378:metabolism
D018995:Myosin Heavy Chains; D009218:Myosins