1. Ciccarelli FD, Alberti S
Structural features of the cysteine-rich region of the Trop molecules
Meeting: BIOCOMP 2000 - Year: 2000
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Abstract: Trop-1 and Trop-2 are homologous transmembrane glycoproteins that are expressed at high levels by most human cancer cells. Trop-1 is induced by cell proliferation and oncogenic transformation, and is a marker of epithelial progenitor cells. Trop-2 is expressed by terminally differentiated epithelial cells and by the placental trophoblast. In the N-terminal region of both molecules there is a large cysteine-rich region (98 residues in Trop-1 and 111 in Trop-2) that is conserved in all the Trop molecules cloned so far. The last six cysteines of this region constitute a typical thyroglobulin domain, while the first six cysteines do not conform to any typical PROSITE pattern. Sequence analysis, secondary structure prediction, fold recognition indicate that an EGF-like domain can be recognized in the region involving the first six cysteines of the Trop molecules. Moreover, the results of sequence analysis show that this sequence module formed by an EGF domain and a thyroglobulin domain is also present in other proteins involved in cell adhesion and in growth control, and hence a role of such a module in these functions can be proposed. The Swiss-PDB-Viewer homology modelling program was employed to build a 3D model of the thyroglobulin domain of the Trop molecules. As a template, we used the thyroglobulin domain of the p41 protein. The RMSD between target and template structures is 1.36 Å. Moreover, 87% of the predicted 3D structure residues fall in the core region of the Ramachandran Plot and 100% in its acceptable region. We are working on the prediction of the 3D structure of the EGF region: joining the two models, a final prediction of the complete cysteine-rich region of the Trop molecules could be obtained.