Medical Sciences Group／Core LaboratoriesTomita N Laboratory
(Laboratory of Biomolecules)
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Associate Professor TOMITA Nono
Protein synthesis is an important process that is fundamental to life. In our laboratory, we elucidate the detailed molecular mechanisms of protein synthesis systems, to understand biological systems from the viewpoint of molecular functions. In addition, we also conduct research on the engineering of protein synthesis systems to generate biopharmaceuticals. We aim to contribute to medical engineering and to develop new diagnostic methods and medical technologies.
- Research
keywords - Protein synthesis, yeast, mitochondria, cell-free translation system, nonnatural amino acids
Biochemistry of protein synthesis system
Utilizing reconstituted protein synthesis systems from E. coli, yeast, and mitochondria, we are analyzing the function of post-translational modifications of translation factors, the role of modified bases in tRNA and mRNA, and the mechanisms of antibiotic action, and so on. Elucidation of the precise regulatory mechanisms of peptide transfer and decoding processes, which are pivotal in protein synthesis, is also important for understanding the pathogenesis of diseases.
Reconstituted yeast translation system (Abe, 2020)
Structural biology of protein synthesis system
Structural biological studies of protein synthesis systems are also conducted. Structural analyses of mitochondrial ribosomes and translation factors are particularly important in drug design and other applications.
Structure of porcine 55S mitoribosome analyzed using CryoArm 300 in Kashiwa II
Engineering of protein synthesis system
We have established a system that can introduce nonnatural amino acids into proteins by applying the yeast cell-free protein synthesis system. By reconstituting all tRNAs in the system with in vitro transcribed tRNAs, we have modified the genetic code, establishing a revolutionary system that can introduce multiple types of nonnatural amino acids into proteins. We are advancing research to utilize this system in the design and development of antibody drugs and other macromolecular pharmaceuticals.
References/papers
- Nucleic Acids Res. (2021) doi: 10.1093/nar/gkaa1165. Reconstitution of mammalian mitochondrial translation system capable of correct initiation and long polypeptide synthesis from leaderless mRNA.
- J Biochem. (2020) doi: 10.1093/jb/mvaa022. In vitro?yeast?reconstituted translation system reveals function of eIF5A for synthesis of long polypeptide.
- J Biochem. (2020) doi: 10.1093/jb/mvaa021. Reconstitution of?yeast?translation elongation and termination in vitro utilizing CrPV IRES-containing mRNA.
- PLoS Genet. (2014) doi: 10.1371/journal.pgen.1004616. Ribosome rescue and translation termination at non-standard stop codons by ICT1 in mammalian mitochondria.
- Nucleic Acids Res. doi: 10.1093/nar/gkt079. Human G-proteins, ObgH1 and Mtg1, associate with the large mitochondrial ribosome subunit and are involved in translation and assembly of respiratory complexes.
- Molecular Cell (2009) doi: 10.1016/j.molcel.2009.06.028. EF-G2mt is an Exclusive Recycling Factor in Mammalian Mitochondrial Protein Synthesis.
