U.S.-Japan Cooperative Research: Molecular Structure of DNA-Protein Complexes

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This award will support a two-year cooperative research project between Professor Alexander Rich, Department of Biology, Massachusetts Institute of Technology, and Professor Yoshimasa Kyogoku, Institute for Protein Research, Osaka University, Japan. The investigators are collaborating in a study of the three- dimensional molecular structure of certain protein-DNA complexes. One complex to be studied will involve the DNA binding portion of the yeast protein gal 4 bound to DNA. The work should shed light on the manner in which the protein recognizes the DNA sequence of its recognition element. This structure is of interest because it incorporates a so-called zinc finger motif, a feature found in a large number of proteins that bind to DNA, and believed to be an important element in DNA-protein recognition. A second protein to be studied is a leucine zipper protein, nuclear factor AP-1, bound to DNA. In both efforts, engineered versions of the DNA binding protein will be synthesized by the Osaka group and the DNA binding elements will be synthesized at MIT. Protein will be mailed to MIT where co-crystallization experiments will be carried out and an x-ray diffraction analysis of the protein-DNA complex completed. Complementary solution NMR studies of both the protein and its complex will be carried out in Osaka. The study should thus yield information on the range of conformations that the protein- DNA system can undergo, and more generally illuminate the important question of the identity or non-identity of biological systems in crystalline and solution form. There is an excellent prospect that this research will lead to a significant contribution to scientific knowledge. The U.S. principal investigator is a highly respected, productive molecular biologist, whose laboratory is one of the top ones in the world for x-ray crystallographic and other structural studies of biological molecules. The Japanese researcher with whom he will cooperate is also an expert in his field. The proposed projects are on the forefront of science and of fundamental importance in understanding the transmission of genetic information and the continuity of viability of an organismal strain.