Mechanism of chaperone function of cyanobacterial Hsp90 and ClpB paralogs
| Project/Area Number |
15K07349
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Applied microbiology
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| Research Institution | Saitama University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 分子シャペロン / 熱ショックタンパク質 / Hsp90 / Hsp70 / ClpB / パラログ / シアノバクテリア / DnaK / DnaJ / HtpG / タンパク質の凝集 / シャペロンネットワーク / Ｈｓｐ９０ / ＨｔｐＧ / ＣｌｐＢ |
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| Outline of Final Research Achievements |
We discovered that HtpG (Hsp90) and DnaK2 (Hsp70) act together to refold denatured proteins in cyanobacteria. In the present study, we found that DnaJ2 physically interacts with HtpG to control its chaperone activity that suppresses aggregation of denatured proteins. DnaJ2 is considered to be the first co-chaperone for HtpG in prokaryotes. We also found a naturally occurring small molecule that inhibits the chaperone function of Hsp90 by enhancing its ATPase activity. Our findings are unexpected because it is assumed that the Hsp90 function is inhibited only when its ATPase is inhibited. As a new project, we worked on cyanobacterial paralogs of ClpB. One of the two paralogs in Synechococcus elongatus, ClpB1, showed biochemical properties similar to E.coli ClpB, whereas ClpB2 was totally different from ClpB1 and E.coli ClpB. I postulate that the clpB2 gene has acquired novel, beneficial functions and becomes preserved by natural selection, with clpB1 retaining the original function.
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| Academic Significance and Societal Importance of the Research Achievements |
真核生物のHsp90のシャペロン作用にとって必須のはたらきをするシャペロン補助因子は、バクテリアではまだ発見されていない。本研究は、DnaJ2がバクテリアHsp90（HtpG）の補助因子としてはたらきうることを初めて示した。また、がん細胞の生存・増殖等に必須とされるHsp90を標的として、Hsp90のATPase活性の阻害剤の探索が行われてきたが、ATPaseの活性化剤によってもシャペロン機能を阻害できることを明らかにした。これは「阻害剤」選択の範囲を広げるものとして重要である。さまざまな生化学的解析を行い、ClpBがシアノバクテリアにおいて独自の進化をしたという新規な仮説を提唱した。
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Report
(5 results)
Research Products
(38 results)
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[Journal Article] Stimulation of the ATPase activity of Hsp90 by zerumbone modification of its cysteine residues destabilizes its clients and causes cytotoxicity.2018
Author(s)
Nakamoto, H., Amaya, Y., Komatsu, T., Suzuki, T., Dohmae, N., Nakamura, Y., Jantan, I., and Miyata, Y.
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Journal Title
Biochemical Journal
Volume: 475
Issue: 15
Pages: 2559-2576
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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