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 filamentous actin and contains sequence repeats that correspond to actin monomers in the filament. Analysis of striated muscle alpha-tropomyosin mutants in which internal sequence has been deleted or replaced with non-tropomyosin sequence showed that the following parameters are important for high affinity, cooperative binding of tropomyosin-troponin to actin. 1) Tropomyosin must be a coiled coil along its entire length. 2) An integral number of repeats corresponding to the actin monomers along its length is more important than the total number. 3) In comparison, the actin affinity is relatively insensitive to changes in the sequence of the internal regions of tropomyosin. The results suggest that the internal sequence repeats function as weakly interacting spacers to allow proper alignment of the ends on the regulated actin filament.
Hitchcock-DeGregori
S E
SE
Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
An
Y
Y
D000199:Actins / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002645:Chickens; D016350:Leucine Zippers; D008961:Models, Structural; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000502:physiology*; D016296:Mutagenesis; D009838:Oligodeoxyribonucleotides; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D014335:Tropomyosin / Q000737:chemistry* / Q000378:metabolism*; D014336:Troponin / Q000378:metabolism
D000199:Actins; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D014335:Tropomyosin; D014336:Troponin