Structural basis for the mechanism of endocytosis involved in oncogenic transformation

• Project/Area Number: 24687014
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Structural biochemistry
• Research Institution: Kyushu University
• Principal Investigator: SHIMADA Atsushi 九州大学, 生体防御医学研究所, 准教授 (70391977)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥27,300,000 (Direct Cost: ¥21,000,000、Indirect Cost: ¥6,300,000); Fiscal Year 2014: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2013: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000); Fiscal Year 2012: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
• Keywords: X線結晶構造解析 / エンドサイトーシス / がん / 脂質膜 / タンパク質

Outline of Final Research Achievements

Endocytosis is a process for eukaryotic cells to internalize extracellular molecules into the cells, which plays an important role in various physiological processes, such as receptor internalization. Endocytosis is also recently implicated in oncogenic transformation. In this study, we performed the structural and functional analyses of endocytic proteins involved in oncogenic transformation. We revealed the mechanism of the recognition of Eps15, which is deeply involved in oncogenic transformation, by SGIP1 and FCHo1, which are key players of the clathrin-assembly step of clathrin-mediated endocytosis. Thus, this study deepens our understanding of the link between oncogenic transformation and endocytosis.

Research Products

• [Journal Article] TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P2 (2014)
  • Author(s): Nobuaki Takahashi, Sayaka Hamada-Nakahara, Yuzuru Itoh, Kazuhiro Takemura, Atsushi Shimada,Yoshifumi Ueda, Manabu Kitamata, Rei Matsuoka, Kyoko Hanawa-Suetsugu, Yosuke Senju, Masayuki X. Mori, Shigeki Kiyonaka, Daisuke Kohda, Akio Kitao, Yasuo Mori and Shiro Suetsugu
  • Journal Title: Nature Communications Volume: 5 Issue: 1 Pages: 4994-4994
  • DOI: 10.1038/ncomms5994
  • NAID: 130005100825
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Crystal structure of the C-terminal globular domain of the third paralog of the Archaeoglobus fulgidus oligosaccharyltransferases. (2013)
  • Author(s): Matsumoto S, Shimada A, Kohda D
  • Journal Title: BMC Struct. Biol. Volume: 13
  • Peer Reviewed
• [Journal Article] Crystal structures of an archaeal oligosaccharyltransferase provide insights into the catalytic cycle of N-linked protein glycosylation. (2013)
  • Author(s): Matsumoto S, Shimada A, Nyirenda J, Igura M, Kawano Y, Kohda D
  • Journal Title: Proc Natl Acad Sci USA Volume: 110 Issue: 44 Pages: 17868-17873
  • DOI: 10.1073/pnas.1309777110
  • Peer Reviewed
• [Presentation] SGIP1 μ homology ドメインによる2つの連続するDPF配列認識機構の構造的基盤 (2014)
  • Author(s): 山口淳子, 神田大輔, 嶋田睦
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-16 – 2014-10-17
• [Presentation] Structural basis for the recognition of Eps15 by the SGIP1 μ homology domain (2014)
  • Author(s): Atsuko Yamaguchi, Daisuke Kohda, Atsushi Shimada
  • Organizer: 23rd congress and general assembly of the international union of crystallography (IUCr2014)
  • Place of Presentation: Montreal
  • Year and Date: 2014-08-11
• [Presentation] SGIP1 μ homology ドメインによるEps15認識機構の構造的基盤 (2014)
  • Author(s): 山口淳子, 神田大輔, 嶋田睦
  • Organizer: 第14回日本蛋白質科学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-06-27
• [Presentation] SGIP1 μ homology domainによるEps15認識機構の構造的基盤 (2014)
  • Author(s): 山口淳子, 神田大輔, 嶋田睦
  • Organizer: 平成26年度日本生化学会九州支部例会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-18
• [Presentation] Crystal structures of an archaeal oligosaccharyltransferase provide insights into the catalytic cycle of N-linked protein glycosylation (2014)
  • Author(s): Shunsuke Matsumoto, Atsushi Shimada, Takahiro Yamasaki, Daisuke Kohda
  • Organizer: 27th International Carbohydrate Symposium
  • Place of Presentation: Bangalore, India
• [Presentation] Structural basis for the recognition of tandem DPF motifs by the SGIP1 μ homology domain (2014)
  • Author(s): Atsuko Yamaguchi, Daisuke Kohda, Atsushi Shimada
  • Organizer: International Symposium between Kyushu University Post-Global Centers of Excellence Program and School of Biomedical Sciences, Monash University
  • Place of Presentation: Melbourne, Australia
• [Presentation] 古細菌型オリゴ糖転移酵素によるN型糖鎖修飾の構造基盤の解明 (2013)
  • Author(s): 松本 俊介, 嶋田 睦, ジェイムス ニレンダ, 井倉 真由美, 河野 能顕, 神田 大輔
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] Cdc42によるCIP4ファミリータンパク質のクラスリン被覆ピットへの局在機構の構造的基盤 (2012)
  • Author(s): 嶋田睦
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-14
• [Presentation] Cdc42によるCIP4のクラスリン被覆ピットへの局在機構の構造的基盤 (2012)
  • Author(s): 嶋田睦
  • Organizer: 第12回日本蛋白質科学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-06-21
• [Remarks] 九州大学ー研究者情報[嶋田 睦]
  • URL: http://hyoka.ofc.kyushu-u.ac.jp/search/details/K004442/
• [Remarks] 生体防御医学研究所構造生物学分野ホームページ
  • URL: http://vsb.bmr.kyushu-u.ac.jp/VSB/index.html
• [Remarks] 九州大学ー研究者情報[嶋田 睦]
  • URL: http://hyoka.ofc.kyushu-u.ac.jp/search/details/K004442/
• [Remarks] 生体防御医学研究所構造生物学分野ホームページ
  • URL: http://vsb.bmr.kyushu-u.ac.jp/VSB/index.html
• [Remarks]
  • URL: http://hyoka.ofc.kyushu-.ac.jp/search/details/K004442/