The relationship between a molecular chaperone and protease : The discovery of NDP kinase like activity of a chaperone, and degeneration diseases.
| Project/Area Number |
14570121
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
YANO Mihiro The University of Tokushima, Institute for Enzyme Research, Associate Professor, 分子酵素学研究センター, 助教授 (40304555)
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| Co-Investigator(Kenkyū-buntansha) |
KIDO Hiroshi The University of Tokushima, Institute for Enzyme Research, Professor, 分子酵素学研究センター, 教授 (50144978)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Hsp70 / Molecular chaperone / Proteasome |
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| Research Abstract |
<The chaperone functions in the ubiquitin-proteasome system>Cellular proteases and molecular chaperones play important roles in the intracellular protein catabolism. The ubiqitin-proteasome system (UPS) is a central component of the quality control mechanism that selectively degrades proteins. Among this pathway, it has been assumed that molecular chaperones activate proteasomal degradation by remodeling the conformation of protein substrate. Previously, we found that the 20S proteasome exhibits an ATP/ADP exchange activity other than proteolytic activities. Here we show that the 20S proteasome protects several heat-denatured proteins as to irreversible aggregation, leading to a maintenance of substrates in an unfolded state for subsequent degradation. Further, we found that VCP plays an important role in mediating the function of the UPS, by interacting with proteasome substrates before they are degraded. <The ATP/ADP exchange activity of Hsp7O and its reaction mechanism>We have previously reported that, in the presence of physiological concentrations of ATP and ADP, Hsp7O catalyses an ATP/ADP exchange reaction. In this study, we characterized the second metal-binding motif by site-directed mutagenesis and the crystal structure of the Hsp7O ATPase domain with bound ATP (Protein Data Bank code for Hsp70 ATPase domain, 1hjo), and found that the second metal-binding site, comprising a loop co-ordinated by His227, Glu231 and Asp232, participates in an ATP/ADP exchange reaction, in co-operation with the first metal-biding site. On the other hand, ADP bound to Hsp70 significantly inhibited the chaperone functionof Hsp70. These results may give an important clue for a better understanding of the ATP/ADP exchange reaction for repeated cycles of substrate binding/release by Hsp70.
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Report
(3 results)
Research Products
(10 results)
