Structural basis of HEAT-kleisin interactions in the condensin I subcomplex
Project/Area Number |
17K07314
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Structural biochemistry
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Research Institution | University of Shizuoka |
Principal Investigator |
Hara Kodai 静岡県立大学, 薬学部, 講師 (80729343)
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Co-Investigator(Kenkyū-buntansha) |
橋本 博 静岡県立大学, 薬学部, 教授 (40336590)
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Project Period (FY) |
2017-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | X線結晶構造解析 / 染色体凝縮 / SMC複合体 / HEAT-kleisin相互作用 / コンデンシン / タンパク質複合体 / タンパク質間相互作用 / 再構成系 / 染色体再構成系 |
Outline of Final Research Achievements |
Condenisn I is a multi-protein complex that plays an essential role in mitotic chromosome assembly and segregation in eukaryotes. It is composed of five subunits: two SMC (SMC2, SMC4), a kleisin (CAP-H), and two HEAT repeat (CAP-D2 and CAP-G) subunits. In this study, the crystal structure of a human condensin I subcomplex comprising CAP-G and CAP-H has been determined. The structure reveal the interaction between CAP-G and CAP-H. Furthermore, CAP-G-H interaction is essential for mitotic chromosome assembly recapitulated in Xenopus egg cell-free extracts.
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Academic Significance and Societal Importance of the Research Achievements |
コンデンシンのHEATリピートサブユニットは両親媒性αヘリックスのペアが多数折り畳まれることで弾力性に富むソレノイド状構造を形成する。この構造モチーフは核酸やタンパク質などの基質と結合することで柔軟な構造変化を誘起し、様々な細胞機能を発揮する。しかし、コンデンシンのHEATリピートサブユニットは原核生物型には存在せず、真核生物型だけに存在する。したがって、その構造基盤を理解することは真核生物がその長大なゲノムDNAをどのように折り畳み制御するのかを理解するための一助となる。さらに、染色体凝縮過程を標的とした新規抗がん剤や抗菌剤、駆虫薬の創出など産業活用にインパクトを与える可能性を秘める。
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Report
(5 results)
Research Products
(94 results)
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[Journal Article] Dynamic feature of mitotic arrest deficient 2-like protein 2 (MAD2L2) and structural basis for its interaction with chromosome alignment maintaining phosphoprotein (CAMP)2017
Author(s)
Hara K, Taharazako S, Ikeda M, Fujita H, Mikami Y, Kikuchi S, Hishiki A, Yokoyama H, Ishikawa Y, Kanno S, Tanaka K, Hashimoto H.
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Journal Title
Journal of Biological Chemistry
Volume: 292
Issue: 43
Pages: 17658-17667
DOI
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Peer Reviewed / Open Access
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[Presentation] Inhibition of GATA4 dimerization suppress hypertrophic responses2019
Author(s)
Satoshi Shimizu, Yoichi Sunagawa, Kodai Hara, Asami Hishiki, Yasufumi Katanasaka, Yusuke Miyazaki, Masafumi Funamoto, Nurmila Sari, Kana Shimizu, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
Organizer
ESC Congress 2019 together with World Congress of Cardilogy
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Int'l Joint Research
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[Presentation] Inhibition of GATA4 dimerization has a potential target for heart failure therapy2019
Author(s)
Satoshi Shimizu, Yoishi Sunagawa, Kodai Hara, Asami Hishiki, Yusuke Miyazaki, Yasufumi Katanasaka, Masafumi Funamoto, Nurmila Sari, Kana Shimizu, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
Organizer
第83回日本循環器学会学術集会
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[Presentation] Inhibition of GATA4 Dimerization Suppresses Cardiac Hypertrophic Responses2018
Author(s)
Satoshi Shimizu, Yoichi Sunagawa, Kodai Hara, Asami Hishiki, Yusuke Miyazaki, Yasufumi Katanasaka, Masafumi Funamoto, Nurmila Sari, Kana Shimizu, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
Organizer
AHA Scientific Session 2018
Related Report
Int'l Joint Research
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[Presentation] Determination and crystallization of GATA4 dimerization domain2018
Author(s)
Satoshi Shimizu, Kodai Hara, Yoichi Sunagawa, Asami Hishiki, Yusuke Miyazaki, Yasufumi Katanasaka, Masafumi Funamoto, Sari Nurmila, Kana Shimizu, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
Organizer
IUBMB Focused Meeting on GATA Transcription Factors
Related Report
Int'l Joint Research
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[Presentation] The acetylation site of GATA4 have an important role for GATA4 dimarization and cardiomyocyte hypertrophy2018
Author(s)
Satoshi Shimizu, Yoichi Sunagawa, Kodai Hara, Asami Hishiki, Yusuke Miyazaki, Yasufumi Katanasaka, Masafumi Funamoto, Nurmila Sari, Kana Shimizu, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
Organizer
第23回 静岡健康・長寿学術フォーラム
Related Report
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[Presentation] Inhibition of GATA4 dimerization is a novel target for heart failure therapy2018
Author(s)
Satoshi Shimizu, Yoichi Sunagawa, Kodai Hara, Asami Hishiki, Yusuke Miyazaki, Yasufumi Katanasaka, Masafumi Funamoto, Nurmila Sari, Kana Shimizu, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
Organizer
The 4th International Conference on Pharma-Food
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[Presentation] GATA4 acetylation site is important for development cardiomyocyte hypertrophy2018
Author(s)
Satoshi Shimizu, Kodai Hara, Yoichi Sunagawa, Asami Hishiki, Masafumi Funamoto, Sari Nurmila, Kana Shimizu, Yusuke Miyazaki, Yasufumi Katanasaka, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
Organizer
23rd Annual Scientific Meeting of the International Society of Cardiovascular Pharmacotherapy
Related Report
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[Presentation] Inhibition of GATA4 Dimerization Suppresses Cardiac Hypertrophic Responses2018
Author(s)
Satoshi Shimizu, Yoichi Sunagawa, Kodai Hara, Asami Hishiki, Yusuke Miyazaki, Yasufumi Katanasaka, Masafumi Funamoto, Nurmila Sari, Kana Shimizu, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
Organizer
日本循環器学会第152回東海・第137回北陸合同地方会
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[Presentation] The dimerization domain of the hypertrophy-responsive transcription factor GATA4 is a therapeutic target for heart failure2018
Author(s)
Satoshi Shimizu, Kodai hara, Yoichi Sunagawa, Asami Hishiki, Masafumi Funamoto, Yusuke Miyazaki, Yasufumi Katanasaka, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
Organizer
第82回日本循環器学会学術集会
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[Presentation] The dimerization domain of GATA4 plays an important role in the development cardiomyocyte hypertrophy2018
Author(s)
Satoshi Shimizu, Kodai Hara, Yoichi Sunagawa, Asami Hishiki, Masafumi Funamoto, Yusuke Miyazaki, Yasufumi Katanasaka, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
Organizer
第1回日本循環器基礎研究フォーラム
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[Presentation] The dimerization domain of GATA4 is a therapeutic target for heart failure2017
Author(s)
Satoshi Shimizu, Kodai Hara, Yoichi Sunagawa, Asami Hishiki, Masafumi Funamoto, Yusuke Miyazaki, Yasufumi Katanasaka, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
Organizer
第22回静岡健康・長寿学術フォーラム
Related Report
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