Cooperative interactions between adjacent troponin-tropomyosin complexes may be transmitted through the actin filament.

Recent analyses of the assembly of thin filaments containing altered forms of troponin (or no troponin) suggested that the strongly cooperative nature of troponin-tropomyosin binding to actin might be primarily caused by indirect interactions involving the actin lattice, rather than by direct contacts between neighboring troponin-tropomyosin molecules. To test this hypothesis, thin filament assembly was examined using either cardiac tropomyosin digested with carboxypeptidase A (cbpTm) or a tropomyosin with defective function at both amino and carboxyl termini (unacetylated cbpTm). Compared to intact troponin-tropomyosin, both troponin-cbpTm and troponin-unacetylated cbpTm had much weaker binding to actin; however, cooperative interactions were only slightly reduced. These data support the implication that the primary source of the cooperativity involves troponin-tropomyosin-promoted conformational changes within the actin polymer. Surprisingly, the effects of tropomyosin amino- and carboxyl-terminal structural defects on troponin-tropomyosin binding to actin were not additive. In the presence of troponin, tropomyosin molecules with either defect had the same diminution in actin affinity as molecules with both defects. Finally, the Ca2+ sensitivity of troponin-tropomyosin binding to actin was increased by alteration of either end of tropomyosin.