Crystallization and Structure Determination of the Human Estrogen Receptor by X-ray Diffraction.

The project is a postdoctoral training fellowship for Dr. Robert Nolte, to support X-ray crystallographic studies of cancer-related macromolecular complexes. (1) We have expressed various constructs of the human estrogen receptor DNA-binding domain, but failed to obtain crystallizable protein. Success of other groups in this and related efforts have led us to focus on different goals. (2) We have prepared crystals of a complex between a six Zn-finger segment of the transcription factor TFIIIA and a 31 bp DNA site. This structure will reveal significant aspects of DNA recognition by Zn-finger proteins, which regulate many loci important for cell growth. (3) During the coming project year, Dr. Nolte will embark on structural studies of Src-related tyrosine kinase activity, as described in the body of the progress report