Research
The most basic activity of life is the transmission of genetic
information "DNA -> mRNA -> protein." This process is strictly
regulated at various levels. In our laboratory, we've been studying
nucleotide-related regulatory mechanisms such as DNA repair, nucleotide
metabolism, and protein modification (post-translational modification).
By combining various methods to analyze the structure and function of
individual proteins, we aims to reveal how these systems that contains
them works.
DNA Repair Systems
Mutations in DNA can threaten life immediately. For example, mutation
of human DNA is one of the major causes of cancer. Therefore, many
proteins are involved in the repair of DNA damages in any organism. In
our laboratory, the thermophilic bacterium Thermus thermophilus HB8,
suitable for structural and functional analysis, is the main subject of
research, and we have studies substrate recognition mechanism and
catalytic mechanism of DNA repair system proteins based on biochemical
analysis and three-dimensional structural information.
Nucleotide Metabolism
In connection with the DNA repair system, we have also studied proteins
involved in the metabolism of nucleic acids and nucleotides. Genomes of
any organism have many genes that are presumed to degrade nucleotides
and their derivatives, but their substrates are unknown. On the other
hand, important enzymes that work in known nucleotide metabolic
pathways have not be found in some genomes. Therefore, we have
identified new enzymes that degrade intracellular signal molecules and
short RNAs by analyzing the structure and function of gene-deficient
strains and proteins in detail. Furthermore, we also found that many of
the enzymes belonging to the nucleotide synthesis pathway are
phosphorylated, and are working on elucidation of their regulatory
mechanisms.
Post-translational Modification
Decoding of the human genome was completed in 2003, and the post-genome
era came, and the center of research spread from DNA to protein. In
addition, advances in mass spectrometry and bioinformatics have made it
possible to rapidly identify protein types and modifications.
Post-translational modifications that add new functions to proteins
beyond genetic information are thought to still have many unknown
metabolic regulatory mechanisms. A number of phosphorylations and
acylations have also been identified in T. thermophilus. In particular,
we have found that in terms of the three-dimensional structure,
residues in the vicinity of the active site or ligand-binding site are
often modified. Therefore, we are working on the elucidation of a new
control mechanism and control network by posttranslational
modification, taking advantage of T. thermophilus that the number of
enzymes responsible for posttranslational modification is small.
Thermus thermophilus as Model Organism
In the hot spring
of Izu in the 1960s, the extremely thermophilic bacterium Thermus
thermophilus HB8 was discovered that would contribute significantly to
the study of proteins. This strain is a type of extremely thermophilic
bacteria that prefer high temperatures around 75 degrees, and is
composed of highly stable proteins that are stable at high
temperatures. It has features suitable for molecular-level research,
such as ease of examining its structure and function, and the small
number of genes (proteins). In addition, since thermophilic bacteria
are close to the root of a phylogenetic tree, they are thought to have
characteristics close to cells that have become common ancestors of all
organisms. Elucidation of the life phenomena found in these extreme
thermophiles at the molecular and atomic level will lead to an
understanding of the vital living mechanisms of all organisms.
Functionally Unknown Proteins
