Troponin C (TNC) is one of the three subunits of the troponin complex (C, I and T) and is the calcium trigger for muscle contraction. Our x-ray structural studies on chicken skeletal troponin C have resulted in a 3.8A map based on two single site derivatives Au and Nd and solvent mask filtering. The molecule is somewhat elongated (48 x 30 x 30A) and is located on the 3(2) axis of the unit cell, space group P3(2)21, a = b = 66.7A, c = 60.8A. Four of the eight helical regions expected in the molecule are visible in the maps and a pair of them are consistent with the well-known EF hand proposed by Kretsinger for Ca binding domains. Further careful heavy atom soaking studies are in progress to obtain another derivative at higher resolution which will enable the complete polypeptide chain to be traced and molecular features such as the four Ca2+ binding domains to be studied. Besides the work on chicken skeletal TNC, we have begun crystallization studies of bovine cardiac TNC. The structural results obtained from the crystallographic studies will provide important information on the nature of the Ca++ binding domains in TNC and allow for a comparison with other known Ca2+ binding proteins, particularly parvalbumin, the intestinal Ca2+ binding protein (Moffatt et al.) and calmodulin (Bugg et al.). The proposed studies will also facilitate the interpretation of the abundant physicochemical data already available on troponin and provide a molecular framework for understanding troponin function in the control of muscle contraction in both health and disease.
| Sundaralingam, M; Sekharudu, Y C; Yathindra, N et al. (1987) Ion pairs in alpha helices. Proteins 2:64-71 |
| Sundaralingam, M; Bergstrom, R; Strasburg, G et al. (1985) Molecular structure of troponin C from chicken skeletal muscle at 3-angstrom resolution. Science 227:945-8 |
| Sundaralingam, M; Drendel, W; Greaser, M (1985) Stabilization of the long central helix of troponin C by intrahelical salt bridges between charged amino acid side chains. Proc Natl Acad Sci U S A 82:7944-7 |
