Life of proteins: maturation, translocation, quality control in the cell
| Project/Area Number |
14037217
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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, Tokyo Institute of Technology, Chemical Resources Laboratory, Professor (90049073)
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| Project Period (FY) |
2002 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥163,000,000 (Direct Cost: ¥163,000,000)
Fiscal Year 2006: ¥32,000,000 (Direct Cost: ¥32,000,000)
Fiscal Year 2005: ¥32,000,000 (Direct Cost: ¥32,000,000)
Fiscal Year 2004: ¥32,000,000 (Direct Cost: ¥32,000,000)
Fiscal Year 2003: ¥30,000,000 (Direct Cost: ¥30,000,000)
Fiscal Year 2002: ¥37,000,000 (Direct Cost: ¥37,000,000)
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| Keywords | GroEL / Prion / Sup35 / ClpB / FtsH / Hsp104 / DnaK / chaperone / 分子シャペロン / シャペロニン / プリオン / 脱凝集 |
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| Research Abstract |
We found an intermediate of GroEL-GroES-assisted protein folding in which substrate protein is tethered to the GroEL's binding sites sharing with GroES. Substrate protein cannot initiate folding in this intermediate until it is release into the cis-cavity. The crystal structure of GroEL-GroES complex with the substrate protein being in cis-cavity. The GroEL ring is deviated from the heptamer symmetry. It was thought that ADP can support chaperonin function but we re-confirmed that only ATP can support folding when ADP was extensively removed from ATP solution.
Sup35, an yeast prion protein, forms a prion fiber. We found Hsp 104 and unkown factor contained in the yeast lysate can break the prion fibers. It is ATP dependent. X-ray diffraction of the prion fibers ondicates that beta helix, rather than widely-believed cross-beta, is a plasusible structure of the fiber.
ClpB is a chaperon that can disaggregate the heat-denatured proteins in an ATP dependent manner with cooperation with DnaK system. We succeeded in crystal structure analysis of ClpB from thermophilic bacteria. A long alfa-helix beside the two nucleotide binding domains features the structure and mechanistic model of disaggregation was proposed. We also determined crystal structures of ATP-dependent protease, FtsH. Protease domain has hexamer symmetry but ATP-binding domains have three fold symmetry. There is a narrow path to reach protease active site from the outside and ATP-driven open-closed motion seems to provide polypeptide pulling reaction.
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Report
(6 results)
Research Products
(26 results)
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[Journal Article] Leu-309 plays a critical role in the encapsulation of substrate protein into the internal cavity of GroEL2006
Author(s)
Koike-Takeshita, A., Shimamura, T., Yokoyama, K., Yoshida, M., Taguchi, H.
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Journal Title
J.Blol.Chem., 281
Pages: 962-967
Related Report
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[Journal Article] β-helix is a likely core structure of yeast prion Sup35 amyloid fibers2004
Author(s)
Kishimoto, A., Hasegawa, K., Suzuki, H., Taguchi, H., Namba K., Yoshida, M.
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Journal Title
Biochem.Biophys.Res.Comm. 315
Pages: 739-745
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[Publications] Lee, S., Sowa, M.E., Watanabe, Y., Sigler, P.B., Chiu, W., Yoshida, M., Tsai, F.T.F: "The Structure of ClpB : A Molecular Chaperone that Rescues Proteins from an Aggregated State"Cell. 115. 229-240 (2003)
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