The crystal structure of tropomyosin filaments has been solved to 15 A resolution by refinement of models against the diffraction data and heavy atom labeling of cysteine residues. These results confirm and extend earlier findings. The improved maps reveal the pitch of the coiled coil, the location of the cysteine residues, and the location and features of the overlapping molecular ends in the filaments. A correlation can now be made between regions of the amino acid sequence and key features of the molecule, such as contact sites in the lattice and departures from regularity along the coiled coil. The crystal shows remarkable dynamic features and the relative flexibility of different parts of the molecule as well as its anisotropic character have been determined. The structure and motions of tropomyosin in the crystal provide information on the structure of tropomyosin in muscle and its possible role in regulation. An atomic model of the molecule has been constructed, based on the low resolution X-ray results, together with the stereochemistry of alpha-helical coiled coils. In contrast to previous views, the molecule appears to display but one set of seven alpha-sites that permit weak linkages of the flexible tropomyosin filament to the actin helix. Correspondingly, we picture that in the "off" state of ATPase activity, the alpha-sites are not occupied; in the "on" state, they are only partly occupied; and in the "potentiated" state, they are more completely saturated. Control of contraction is therefore seen as a statistical mechanism requiring at least three distinct average conformations for the tropomyosin molecule on the actin helix.

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Journal Article

Authors

Phillips GN, Fillers JP, Cohen C

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