INTEGRAL REPEATS AND A CONTINUOUS COILED-COIL ARE REQUIRED FOR BINDING OF STRIATED-MUSCLE TROPOMYOSIN TO THE REGULATED ACTIN FILAMENT

Tropomyosin is a coiled-coil protein that binds along the length of fi lamentous actin and contains sequence repeats that correspond to actin monomers in the filament. Analysis of striated muscle alpha-tropomyos in mutants in which internal sequence has been deleted or replaced wit h non-tropomyosin sequence showed that the following parameters are im portant for high affinity, cooperative binding of tropomyosin-troponin to actin. 1) Tropomyosin must be a coiled coil along its entire lengt h. 2) An integral number of repeats corresponding to the actin monomer s along its length is more important than the total number. 3) In comp arison, the actin affinity is relatively insensitive to changes in the sequence of the internal regions of tropomyosin. The re suits suggest that the internal sequence repeats function as weakly interacting spa cers to allow proper alignment of the ends on the regulated actin fila ment.