2006 Fiscal Year Final Research Report Summary
Life of proteins: maturation, translocation, quality control in the cell
| Project/Area Number |
13053101
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
YOSHIDA Masasuke Tokyo Institute of Technology, Chemical Resources Laboratory, Professor (90049073)
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| Co-Investigator(Kenkyū-buntansha) |
ENDO Toshiya Nagoya University, Grad.Sch.Science, Professor (70152014)
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| Project Period (FY) |
2001 – 2007
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| Keywords | molecular chperone / ER stress / translocation / prion / ERAD / lipoprobin / disulfidebond formation / ATP dependent protease |
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| Research Abstract |
Crystal structure of DsB-DsbA complex was determined. The structure provided the basic knowledge to understand the mechanism of disulfide bond generation at the peripheral space of bacteria. The mechanismis proposed that DsbA gained the oxidation ability through cysteine rearrangement of DsbB. As a key factor of endplasmic reticurum-associated degradation (ERAD), Man8 rectin-like factor, EDEM was found. EDEM stimulates degradation of misfolded proteins in a mannose-trimming-dependent manner. Atg5 knock-out mouse died after the birth with nutritional diffuclty. The mouse already accumulated ubiquitin-positive inclusion body in liver cells and nerve cells before birth. The time sequence of stress-response of ER is elaborately designed; at first ATF6 induces the synthesis of molecular chaperones to rescue dameaged proteins, and next XBP1 starts to stimulate the synthesis of EDEM and Derlin-2 for degaradation of misfolded proteins. Crystal structures of soluble domains of FtsHwas determined. The structure indicates the cooperation of between adjacent subunits and existence of narrow path to the protease active site. The structure of C1pB, a critical disaggregation chaperone, was also determined. Two-timer model was proposed from the single molecule observation of GroEL and GroES reaction cycles. The understanding of bacterial outer membrane protein sorting system (Lo1) has made great progress. The structures of Lo1A and Lo1B were determined. The genes responsible for human peroxisome diseases were characterized. It was found that eukaryotic chaperonin contribute to the blocking the formation of polyglutamine aggregates and protect the nerve cells. It was also found that Yeast prion Sup32 fiber is broken by Hsp104 and unknown factor.
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Research Products
(10 results)
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[Journal Article] Crystal structure of the DsbB-DsbA complex reveals a mechanism of disulfide bond generation.2006
Author(s)
Inaba, K., Murakami, S., Suzuki, M., Nakagawa, A., Yamashita, E., Okada, K., Ito, K.
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Journal Title
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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