| Project/Area Number |
10179102
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas (A)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Yokohama City University (2001)
Nara Institute of Science and Technology (1998-2000) |
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Principal Investigator |
SHIRAKAWA Masahiro Yokohama City University, professor, 大学院・総合理学研究科, 教授 (00202119)
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| Co-Investigator(Kenkyū-buntansha) |
HORIKOSHI Masami Tokyo University, Associate Professor, 分子細胞生物学研究所, 助教授 (70242089)
FUJITA Takashi The Tokyo Metropolitan Institute of Medical Science, Group Leader, 室長 (10156870)
NISHIMURA Yoshibumi Yokohama City University, professor, 大学院・総合理学研究科, 教授 (70107390)
KATAHIRA Masato Yokohama National University, Associate Professor, 大学院・環境情報研究院, 助教授 (70211844)
NAKAJIMA Shinsuke Osaka University, Research Associate, 蛋白質研究所, 助手 (60324852)
中村 春木 大阪大学, 蛋白質研究所, 教授 (80134485)
松尾 浩 大阪大学, 蛋白質研究所, 助手 (60304052)
梅園 和彦 京都大学, ウイルス研究所, 教授 (50183752)
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| Project Period (FY) |
1998 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥113,200,000 (Direct Cost: ¥113,200,000)
Fiscal Year 2001: ¥26,400,000 (Direct Cost: ¥26,400,000)
Fiscal Year 2000: ¥29,700,000 (Direct Cost: ¥29,700,000)
Fiscal Year 1999: ¥27,400,000 (Direct Cost: ¥27,400,000)
Fiscal Year 1998: ¥29,700,000 (Direct Cost: ¥29,700,000)
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| Keywords | transcription / protein structure / chromatin / NMR / X-ray crystallography / X線結晶構造解析 / 転写 / 蛋白質 / 立体構造 / 遺伝子修復 / NMR / 基本転写因子 / クロマチン / DNA結 / G蛋白質共役受容体 / 水素結合 / X線 / 蛋白質-蛋白質相互作用 / 蛋白質の立体構造 |
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| Research Abstract |
Through close collaborations between members of this grant group, many new findings in the field of transcription, DNA repair and chromatin remodeling were reported. One of them is the structure of the complex between the methyl-CpG-binding domain of MBD1 and a methylated DNA, by Shirakawa and co-workers. CpG methylation in vertebrates is important for the regulation of gene activity, genomic stability and chromatin structure ; differences in the DNA-methylation status are associated with imprinting phenomena, development, and carcinogenesis. Methylation signals are interpreted by protein factors that contain methyl-CpG-binding domains (MBDs). Shirakawa and co-wokers have determined solution structure of the MBD of the human methylation-dependent transcriptional regulator MBD1 bound to a methylated DNA. The methyl groups at the methylation site are recognized through extensive hydrophobic contacts with aliphatic and aromatic portions of arginine, tyrosine, and serine residues that are totally conserved among the MBD family. Discrimination of the CG sequence is due to the sama arginine and tyrosine residues. The structure indicates how MBD may access to nucleosomal DNA without encountering steric interference from core histones. It also suggests that some residues of MeCP2 that are mutated in Rett syndrome are located at the protein-DNA interface, providing a structural basis to understand the consequence of these mutations.
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