Modulation of myosin function by isoform-specific properties of Saccharomyces cerevisiae and muscle tropomyosins

Tropomyosin is an extended coiled-coil protein that influences actin functi on by binding longitudinally along thin filaments. The present work compare s cardiac tropomyosin and the two tropomyosins from Saccharomyces cerevisia e, TPM1 and TPM2, that are much shorter than vertebrate tropomyosins. Unlik e cardiac tropomyosin, the phase of the coiled-coil-forming heptad repeat o f TPM2 is discontinuous; it is interrupted by a 4-residue deletion. TPM1 ha s two such deletions, which flank the 38-residue partial gene duplication t hat causes TPM1 to span five actins instead of the four of TPM2. Each of th e three tropomyosin isoforms modulates actin-myosin interactions, with isof orm-specific effects on cooperativity and strength of myosin binding. These different properties can be explained by a model that combines opposite ef fects, steric hindrance between myosin and tropomyosin when the latter is b ound to a subset of its sites on actin, and also indirect, favorable intera ctions between tropomyosin and myosin, mediated by mutually promoted change s in actin. Both of these effects are influenced by which tropomyosin isofo rm is present. Finally, the tropomyosins have isoform-specific effects on i n vitro sliding speed and on the myosin concentration dependence of this mo vement, suggesting that non-muscle tropomyosin isoforms exist, at least in part, to modulate myosin function.