We present a model of the actin-tropomyosin complex in which the radial and azimuthal position of tropomyosin was adjusted to fit the X-ray fiber diffraction patterns from oriented actin-tropomyosin gels at a resolution of 8 Angstroms. We used the recently published atomic F-actin model for the calculations. The atomic model of tropomyosin was obtained by model-building a coiled-coiled structure from the tropomyosin sequence. The resulting atomic model is strongly preferred and shows strong electrostatic interactions between the charged side-chains of tropomyosin residues and actin residues in subdomain 3 and 4. Furthermore, calculations of enthalpies based upon electrostaic interactions indicate that there is a favored rotational position of the tropomyosin core at the calculated position given by X-ray refinement. Rotations of the tropomyosin strand out of this position turn strongly attractive electrostatic interactions into repulsive forces. The resulting binding radius of 39 Angstroms and the azimuthal position of tropomysoin are in good agreement with electron microscopy reconstructions and neutron diffraction experiments. Furthermore, the calculated position of tropomyosin would still partly block the rigor interaction of myosin cross-bridges with actin, whereas it very likely allows undisturbed binding of the cross-bridges in a weak binding state. The UCSF MidasPlus program was used extensively in this project to visualize the proposed actin-tropomyosin complex. The software proved especially powerful in the display and manipulation of this very large protein complex, and the user interface was both easy to learn and well documented.
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