Protein conformational changes and molecular chaperone

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In order to understand how protein tertiary structure that is responsible for biofunction occurs and how molecular chaperones are involved in the event, we studied stabilities and conformational changes of various proteins, and clarified molecular mechanism of protein amyloid fibril formation. Furthermore, we studied functional mechanism of molecular chaperone, especially, chaperonins in detail, and obtained following results.1. Study on chaperonin mechanism: We have studied in detail structure and function relationship of group I chaperonin GroEL from E. coli and group II chaperonins from hyper-thermostable strains, from protein science and biophysical points of view. We have found that domain movements of GroEL are very important for the function and that cobalt and manganese ions are novel factors for nucleotide hydrolysis activity and substrate refolding function of group II chaperonin.2. Study on mechanism of protein amyloid fibril formation: We have found that oligomeric protein … More GroES, that is a non-related protein to disease, formed typical amyloid fibrils under unfolded conditions, and elucidated the fibril formation mechanism in terms of molecular compactness. Furthermore, we studied fibril formation mechanism of α-synuclein, that is a causative protein of Parkinson's disease, and proved that the amyloid fibril formation of α-synuclein is accelerated markedly in the presence of preformed seeds of other different protein's fibrils.3. Study on structure and stability of oligomeric protein: We have determined the X-ray crystal structure of thermostable aspartase enzyme, and elucidated the mechanism of thermostability and active site structure of the enzyme comprising from 4 identical subunits. On the other hand, we studied solution structure and molecular unfolding mechanism of E. coli co-chaperonin GroES heptamer at high protein concentrations by using small angle X-ray scattering. Furthermore, we clarified that the subunit interaction is quite important for the total structural stability. Less