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

该奖项将支持麻省理工学院生物系Alexander Rich教授和日本大阪大学蛋白质研究所Yoshimasa Kyogoku教授之间为期两年的合作研究项目。研究人员正在合作研究某些蛋白质- dna复合物的三维分子结构。要研究的一个复合体将涉及酵母蛋白gal 4与DNA结合的DNA结合部分。这项工作应该阐明蛋白质识别其识别元件的DNA序列的方式。这种结构之所以引起人们的兴趣，是因为它包含了一个所谓的锌指基序，这是一种在大量与DNA结合的蛋白质中发现的特征，被认为是DNA-蛋白质识别的重要元素。第二种要研究的蛋白质是一种与DNA结合的亮氨酸拉链蛋白，核因子AP-1。在这两项工作中，DNA结合蛋白的工程版本将由大阪小组合成，DNA结合元件将在麻省理工学院合成。蛋白质将邮寄到麻省理工学院，在那里将进行共结晶实验，并完成蛋白质- dna复合物的x射线衍射分析。蛋白质及其复合物的互补溶液核磁共振研究将在大阪进行。因此，这项研究应该提供蛋白质- DNA系统可以经历的构象范围的信息，并更普遍地阐明在晶体和溶液形式下生物系统的同一性或非同一性的重要问题。这项研究很有可能对科学知识作出重大贡献。美国首席研究员是一位备受尊敬的多产分子生物学家，他的实验室是世界上x射线晶体学和其他生物分子结构研究的顶级实验室之一。与他合作的那位日本研究人员也是他所在领域的专家。拟议的项目处于科学的前沿，对理解遗传信息的传递和生物体菌株生存能力的连续性具有根本的重要性。

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.