| Project/Area Number |
16K07277
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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 |
Structural biochemistry
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| Research Institution | Yokohama City University |
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Principal Investigator |
Okuda Masahiko 横浜市立大学, 生命医科学研究科, 特任准教授 (60448686)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 基本転写因子 / RNAポリメラーゼ / 複合体 / NMR / 立体構造 / タンパク複合体 / RNAポリメラーゼII / 構造生物学 |
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| Outline of Final Research Achievements |
A subunit of the general transcription factor TFIIH, p62 plays an important role in recruiting TFIIH to functional sites by binding to various transcription and DNA repair factors. We have utilized structural information on the complexes of p62 with the binding partners: the general transcription factor TFIIEα, the tumor suppressor p53 and the DNA repair factor XPC, and identified a new partner, a subunit protein of RNA polymerase II (Pol II). In this study, we have determined the structures of the Pol II-subunit and its complex with p62 by using NMR and revealed the recognition mechanism. Furthermore, we have prepared several Pol II-subunit mutants, in which residues important for the binding are replaced with alanine and performed binding analyses for the mutants by using NMR and ITC. Remarkable loss of the binding ability of the mutants has validated the structure we solved.
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| Academic Significance and Societal Importance of the Research Achievements |
遺伝子情報の読み出し（転写）は生命の根幹をなす極めて重要な反応であり、その機構の解明には転写装置の立体構造情報が不可欠なため、世界中で精力的に構造研究が進められている。今回の我々の結果は、TFIIHとPol IIの相対配置に関する構造情報を提供するものであり、世界で進行中の転写装置の構造モデル化、反応機構の解明に多大に貢献する。
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