Molecular mechanism of ribosome hijack by the HCV IRES
Project/Area Number |
16H04756
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Structural biochemistry
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Research Institution | Institute of Physical and Chemical Research |
Principal Investigator |
Ito Takuhiro 国立研究開発法人理化学研究所, 生命機能科学研究センター, ユニットリーダー (70401164)
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Research Collaborator |
IMATAKA hiroaki
SHIGEMATSU hideki
YOKOYAMA takeshi
KASHIWAGI kazuhiro
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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Keywords | ウイルス / 生体分子 / 電子顕微鏡 / 翻訳 / 翻訳開始 |
Outline of Final Research Achievements |
We determined the cryo-EM structure of the HCV IRES which binds to the 40S ribosomal subunit of the translating 80S ribosome without impeding the ongoing translation. Single-molecule measurements by fluorescence microscopy confirmed that the HCV IRES binds to the translating ribosome. Additional cryo-EM studies showed that the HCV IRES binds to the 40S subunit of the translating 80S ribosome even in the case of the HCV IRES-dependent translation. Biochemical experiments showed that the ribosome translating cap-dependently is a better substrate for the HCV IRES than a free ribosome.
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Academic Significance and Societal Importance of the Research Achievements |
HCV由来のIRESがこれまで想定されていなかった方法で反応中の翻訳装置リボソームを乗っ取っていることを示した点で画期的である。本研究により明らかになった機構は、HCV由来のIRESと同じような構造を持つ他のウイルスにも共通すると考えられる。従って、IRESとリボソームの40Sサブユニットとの相互作用を阻害する薬剤を開発できれば、効果的な抗ウイルス薬になる可能性がある。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] HCV IRES captures an actively translating 80S ribosome2019
Author(s)
Yokoyama Takeshi、Machida Kodai、Iwasaki Wakana、Shigeta Tomoaki、Nishimoto Madoka、Takahashi Mari、Sakamoto Ayako、Yonemochi Mayumi、Harada Yoshie、Shigematsu Hideki、Shirouzu Mikako、Tadakuma Hisashi、Imataka Hiroaki、Ito Takuhiro
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Journal Title
Molecular Cell
Volume: 印刷中
Issue: 6
Pages: 1205-1214
DOI
Related Report
Peer Reviewed / Open Access
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