Mechanism of Selective Degradation of Proteins

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To analyze mechanisms for selective intracellular protein degradation, two major protease systems in cells, proteasome and calpain, were mainly studied. Suzuki succeeded to analyze the crystal structure of calpain at 2.3Å and found that calpain exists as an inactive proenzyme which requires Ca-induced large conformational changes to become active. Domain III of unknown function is responsible for the Ca-induced conformational changes and translocation to biological membrane. Maki identified 4 novel calpastatin species produced by alternative splicing. Tanaka identified 5 alternative splicing variants of poly-ubiquitin receptor of 26S proteasome differently expressed in various tissues and thus showed distinct functions. A novel proteasome species responsible for endogenous antigen processing containing catalytic and regulatory subunits distinct from 26S proteasome was discovered and named immune proteasome. Further, the gene product for Parkinsonism was identified to be ubiquitin ligase suggesting that the deposition of its target protein of the ligase would be the cause of the disease. Yamao identified a novel proteolytic system of fission yeast for degradation of M phase cyclin containing novel E2. Murakami clarified the molecular mechanism for binding and degradation of ornithine decarboxylase by proteasome and the function of antizyme and ATP in the process. Kido analyzed molecular basis for influenza virus infection to host cells that requires specific degradation of virus membrane proteins by host cell tryptase clara. A specific inhibitor protein for clara tryptase was also fund.