Protein-protein interaction in intracellular signal transduction

本研究的目的是从蛋白质和蛋白质复合体的三维结构出发，阐明细胞内的信号转导。为此，我们组织了三个小组，第一个小组涉及细胞内信号转导，包括肌动蛋白细胞骨架和生长因子受体信号的调节机制。第二组是研究核内的信号转导，那里的信号是由共激活剂整合的。第三组集中于新技术的发展，以阐明蛋白质-蛋白质的相互作用，并建立高通量结构的核磁共振测定方法。由于跨学科研究的性质，分子生物学家、细胞生物学家和结构生物学家加入了每个小组。还组织了督导小组，确定研究方向，促进各小组之间的合作。在本研究项目中，从1998年到2001年，在四年的时间里进行了大量的联合研究，确定了80多个蛋白质及其配体-蛋白质络合物的新结构，并在国际知名期刊上发表了论文。我们邀请了许多青年科学家作为这个项目的成员。我们还组织了核磁共振研讨会，邀请了剑桥大学的詹姆斯·基勒博士，他以教授基本的核磁共振概念和先进的核磁共振技术而闻名。该研究项目不仅极大地促进了跨学科领域的知识交流，而且也促进了日本结构生物学的发展。

The aim of the present research project is to elucidate the intracellular signal transduction based on the three dimensional structure of proteins and protein complexes. For this purpose, we organized three groups ; The first group was concerned with the intracellular signal transduction including regulational mechanism of actin cytoskeleton and growth factor receptor signaling. The second group was to investigate the signal transduction in the nucleus, where signals were integrated by co-activators. The third group focused on the development of new techniques to elucidate the protein-protein interaction and to establish the method for high-throughout structural determination by NMR. Owing to the nature of interdisciplinary research, molecular biologists, cell biologists and structural biologists joined each group. The supervising group was also organized to set up the research directions and to promote collaborations among each group. In the present research project, a number of joint researches were made in four years from 1998 till 2001 and more than 80 novel structures of proteins and ligand-protein complexes were determined and published in distinguished international journals. We invited many young scientists as members of the project. We also organized NMR workshops where we invited Dr. James Keeler of Cambridge University who has reputation for teaching basic NMR concepts and advanced NMR techniques. The research project contributed significantly not only to promote the exchange of knowledge of interdisciplinary areas but also to develop structural biology in Japan.