Structural and functional studies on biological macromolecules involved in the flow of genetic information and the cellular signal transduction.

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To understand in detail the systems of genetic expression and cellular signal transduction, which consist of cascades of macromolecular interactions, molecular interactions involved in the cascades were analyzed at atomic resolutions by crystallography. We targeted post-transcriptional tRNA processing and modification enzymes and aminoacyl-tRNA synthetases, which are responsible for accurate joining tRNA and amino acid during translation, and performed structural analyses of their complexes with tRNAs, other substrates, and/or inhibitors. We also determined the crystal structure of Vasa, an RNA helicase involved in the differentiation of Drosophila germline, and elucidated structural basis of the RNA double strand resolution by a DEAD-box RNA helicase. Furthermore, we succeeded in crystal structure determination of RNA polymerase and Dmc1, which play central roles in transcription and homologous recombination in meiosis, respectively. The structural information was applied to develop the artificial genetic code system to incorporate a useful, natural or non-natural amino acid into a specific position of any protein. We have established systems to incorporate tyrosine or lysine derivatives, and thus opened a way to the technology that facilitates incorporating an amino acid possessing fluorescent, reactive, or heavy-atom containing groups.