Functomics Biology II Research Team
Team Leader
Yoshitaka BESHHO (Ph.D.)
The mission of this team is to accomplish the complete elucidation of intracellular subsystems, through structural and functional analyses. We are focusing on the "protein-synthesis (translation)" and "DNA-repair" subsystems, as essential cellular processes in the central-dogma of life. The protein-synthesis system is the most important cellular operation. Translation is a compiling system, from the genetic information of the DNA to the amino-acid chain of the protein. The translator molecule is "tRNA", the place of translation is the "ribosome", and the rule of translation is the "genetic code". tRNA is a key molecule of the protein synthesis system, and thus we are focusing on the enzymes related to tRNA maturation and aminoacylation. In addition, as an example of a ribosomal system, a quality-control system has been extensively analyzed in the project. In terms of genomic integrity, a vast amount of DNA damage occurs from UV radiation, various chemical reagents, and errors during DNA replication and genetic recombination. These DNA lesions are very harmful, and can result in mutagenesis and even cell death. To remove these lesions, cells have various types of DNA-repair systems, and most of them are common to many organisms, including humans. Through structural and functional analyses as well as basic research in cell imaging, this research team aims to understand the cellular systems in the extremely thermophilic model organism, Thermus thermophilus HB8. This team is developing cutting-edge technologies of bio-molecular imaging, facilitated by new generation pulsed coherent X-rays. Since the proteins from T. thermophilus are stable in a vacuum, we can develop the technology to place a protein molecule onto a DNA molecule in a vacuum. This technology should contribute to single-molecule imaging in the near future, as strong biological applications of the X-ray free electron laser (XFEL) at the SPring-8 site.
- Structural and functional analyses of proteins involved in protein-sysnthesis systems
- Structural and functional analyses of proteins involved in DNA-repair systems
- Fuctional discovery of functionally-unknwon proteins involved in central-dogma system
- In vitro resonctruction of "tRNA-maturation"and "DNA-repair" systems
- Developmental researches for the bio-molecule imaging with the synchrotoron and XFEL technologies
- Kuratani M., Hirano M., Goto-Ito S., Itoh Y., Hikida Y., Nishimoto M., Sekine S., Bessho Y., Ito T., Grosjean H., and Yokoyama S.
"Crystal structure of Methanocaldococcus jannaschii Trm4 complexed with sinefungin."
J. Mol. Biol. 401, 323-333 (2010) - Nakane, S., Nakagawa, N., Kuramitsu, S., and Masui R.
"Characterization of DNA Polymerase X from Thermus thermophilus HB8 Reveals the POLXc and PHP Domains are both Required for 3'-5' Exonuclease Activity."
Nucleic Acids Res. 37, 2037-2052 (2009) - Bessho Y and Yokoyama S.
"Enzymatic formation of 5-aminomethyl-uridine derivatives in tRNA."
In: Henri Grosjean (ed) DNA and RNA modification enzymes. Landes Bioscience, Austin, pp.409-425 (2009) - Ihsanawati, Nishimoto M., Higashizima K., Shirouzu M., Grosjean H., Bessho Y. , and Yokoyama S.
"Crystal structure of tRNA N2, N2-guanosine dimethyltransferase Trm1 from Pyrococcus horikoshii."
J. Mol. Biol. 383, 871-884 (2008) - Agari Y., Sato S., Wakamatsu T., Bessho Y., Ebihara A., Yokoyama S., Kuramitsu S., and Shinkai A.
"X-ray crystal structure of a hypo- thetical Sua5 protein from Sulfolobus tokodaii strain 7."
Proteins 70, 1108-1111 (2008) - Fukui, K., Nakagawa, N., Kitamura, Y., Nishida, Y., Masui, R., and Kuramitsu, S.
"Crystal Structure of MutS2 Endonuclease Domain and the Mechanism of Homologous Recombination Supression."
J. Biol. Chem. 283, 33417-33427 (2008) - Fukui, K., Nishida, M., Nakagawa, N., Masui, R., and Kuramitsu, S.
"Bound Nucleotide Controls the Endonuclease Activity of Mismatch Repair Enzyme MutL."
J. Biol. Chem. 283, 12136-12145 (2008) - Morita, R., Ishikawa, H., Nakagawa, N., Kuramitsu , S., and Masui, R.
"Crystal Structure of a Putative DNA Methylase TTHA0409 from Thermus thermophilus HB8"
Proteins 73, 259-264 (2008) - Bessho Y., Shibata R., Sekine S., Murayama K., Higashizima K., Hori-Takemoto C., Shirouzu M., Kuramitsu S., and Yokoyama S.
"Structural basis for functional mimicry of long-variable- arm tRNA by transfer-messenger RNA."
Proc. Natl. Acad. Sci. USA 104, 8293-8298 (2007) - Kosaka, H., Hoseki, J., Nakagawa, N., Kuramitsu, S., and Masui, R.
"Crystal Structure of Family 5 Uracil-DNA Glycosylase Bound to DNA"
J. Mol. Biol. 373, 839-850 (2007)
Principal Investigator
- Yoshitaka BESSHO
- Team Leader
Staff Scientist
- Tsutomu MIKAWA
- Aya KITAMURA
- Research Scientist