| Project/Area Number |
10680579
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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 |
Structural biochemistry
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| Research Institution | NIIGATA UNIVERSITY |
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Principal Investigator |
ODANI Shoji Faculty of Science, NIIGATA UNIVERSITY, Professor, 理学部, 教授 (60018702)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | fatty acid-binding protein / isoaspartate / cysteine / glutathione / mixed disulfide / proteolysis / amyloid / proteinase inhibitor / 酸化ストレス / 蛋白質エイジング / タンパク質 / 翻訳後修飾 / プロテアーゼ / プロテアーゼ インヒビター / チオール基 / 蛋白質代謝 |
|---|
| Research Abstract |
A number of cellular functions are regulated through proteolysis, and mechanism of selective proteolysis of intra-and extra-cellular proteins has been intensively studied. Although the idea that post-translational modifications determine half-lives of proteins has long been proposed, there is no convincing experimental verification. This project has established that mixed disulfide formation with glutathione, the physiologically most important thiol compound, greatly increases proteolytic susceptibility of cellular fatty acid-binding proteins. Many cellular proteins contain free cysteine residues of unknown function, and thiol-disulfide interchange at these cysteine residues may be a ubiquitous mechanism for cellular protein degradation. We also found rat cutaneous fatty acid-binding protein and a fish liver fatty acid-binding protein contain disulfide bonds despite their cytosolic origin. This finding suggests an intramolecular thiol-disulfide interchange mechanism for regulation of the proteolysis and functions of such proteins. Rat liver fatty acid-binding protein undergoes transpeptidation reaction at Asn-Gly (residue105 and 106). The modified protein also readily digested by proteinases. Because rate of the isoaspartate formation depends onthe franking sequence, this modification may also determine the half-life of individual protein. Limited proteolysis of a normally soluble protein sometimes leads to amyloid fibril formation. Factors affecting such proteolysis was also investigated by structural analysis of an amyloidgenic light chain. A novel regulatory mechanism of proteolysis by the active-inactive conformational transition of a proteinase inhibitor was also found by the present project.
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