Structural basis of the autophagy-specific E1 enzyme Atg7

2013 Fiscal Year Final Research Report

• Project/Area Number: 23687012
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Structural biochemistry
• Research Institution: Microbial Chemistry Research Foundation
• Principal Investigator: NODA Nobuo 公益財団法人微生物化学研究会, 微生物化学研究所, 主席研究員 (40396297)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: オートファジー / Atg7 / E1酵素 / 構造生物学 / 結晶構造

Research Abstract

The crystal structure of Atg7, the E1 enzyme specific to autophagy, has been determined alone and in complex with various Atg factors. Using the structural information, mutational analyses were performed, which revealed that Atg7 recognizes ubiquitin-like proteins and E2 enzymes using unique structures that were not observed in other E1 enzymes and that Atg7 catalyzes the conjugation reaction between ubiquitin-like proteins and E2 enzymes using a novel mechanism that has never been observed in other E1 enzymes. Since the reactions catalyzed by Atg7 are essential only to autophagy, the obtained knowledge will contribute to the development of novel compounds that specifically regulate autophagy.

Research Products

• [Journal Article] Atg12-Atg5 conjugate enhances E2 activity of Atg3 by rearranging its catalytic site (2013)
  • Author(s): Sakoh-Nakatogawa, M., Matoba, K., Asai, E., Kirisako, H., Ishii, J., Noda, N. N., Inagaki, F., Nakatogawa, H. and Ohsumi, Y
  • Journal Title: Nature Structural & Molecular Biology Volume: Vol.20 Pages: 433-439
  • DOI: 10.1038/nsmb.2527
  • Peer Reviewed
• [Journal Article] Structure of the Atg12-Atg5 conjugate reveals a platform for stimulating Atg8-PE conjugation (2013)
  • Author(s): Noda, N. N., Fujioka, Y., Hanada, T., Ohsumi, Y. and Inagaki, F
  • Journal Title: EMBO Reports Volume: Vol.14 Pages: 206-211
  • DOI: 10.1038/embor.2012.208
  • Peer Reviewed
• [Journal Article] オートファジーの構造生物学 (2013)
  • Author(s): 野田展生
  • Journal Title: 生化学 Volume: Vol.85 Pages: 762-774
  • URL: http://www.jbsoc.or.jp/seika/wp-content/uploads/2014/06/85-09-04.pdf
• [Journal Article] オートファジーの構造生物学主要Atg因子の構造の最新像と未解決課題 (2013)
  • Author(s): 野田展生
  • Journal Title: 実験医学 Volume: Vol.31 Pages: 1355-1361
• [Journal Article] Non-canonical recognition and Ubl-loading of distinct E2s by autophagy-essential Atg7 (2012)
  • Author(s): Yamaguchi, M., Matoba, K., Sawada, R., Fujioka, Y., Nakatogawa, H., Yamamoto, H., Kobashigawa, Y., Hoshida, H., Akada, R., Ohsumi, Y., Noda, N. N. and Inagaki, F
  • Journal Title: Nature Structural & Molecular Biology Volume: Vol.19 Pages: 1250-1256
  • DOI: 10.1038/nsmb.2451
  • Peer Reviewed
• [Journal Article] Structural insights into Atg10-mediated formation of the autophagy-essential Atg12-Atg5 conjugate (2012)
  • Author(s): Yamaguchi, M., Noda, N. N., Yamamoto, H., Shima, T., Kumeta, H., Kobashigawa, Y., Akada, R., Ohsumi, Y. and Inagaki, F
  • Journal Title: Structure Volume: Vol.20 Pages: 1244-1254
  • DOI: 10.1016/j.str.2012.04.018
  • Peer Reviewed
• [Journal Article] Atg7とそのAtg8結合型の立体構造 (2012)
  • Author(s): 野田展生
  • Journal Title: 日本結晶学会誌 Volume: 54 Pages: 166-171
  • DOI: 10.5940/jcrsj.54.166
  • Peer Reviewed
• [Journal Article] Structural basis of Atg8 activation by a homodimeric E1, Atg7 (2011)
  • Author(s): Noda, N. N., Satoo, K., Fujioka, Y., Kumeta, H., Ogura, K., Nakatogawa, H., Ohsumi, Y. and Inagaki, F
  • Journal Title: Molecular Cell Volume: Vol.44 Pages: 462-475
  • DOI: 10.1016/j.molcel.2011.08.035
  • Peer Reviewed
• [Presentation] 構造生物学と生化学から迫るオートファジーの分子機構 (2013)
  • Author(s): 野田展生
  • Organizer: 平成25年度日本生化学会関東支部例会
  • Place of Presentation: 山梨大学甲府キャンパス(山梨県甲府市)
  • Year and Date: 2013-06-15
• [Presentation] Structural insights into ubiquitin-like modifications essential for autophagy (2013)
  • Author(s): Nobuo N. Noda
  • Organizer: 2013 KSBMB Annual Meeting
  • Place of Presentation: COEX (Seoul, Korea)
  • Year and Date: 2013-05-15
• [Presentation] オートファジーに必須なAtg結合系の構造基盤 (2012)
  • Author(s): 野田展生
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場(福岡市)
  • Year and Date: 2012-12-14
• [Presentation] オートファジーの構造生物学的研究 (2012)
  • Author(s): 野田展生
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場(福岡市)
  • Year and Date: 2012-12-14
• [Presentation] Structure and function of the autophagy-essential E1, Atg7 (2012)
  • Author(s): Nobuo N. Noda
  • Organizer: 6th International Symposium on Autophagy : Molecular Mechanism, Cellular and Physiological Functions and Diseases
  • Place of Presentation: Bankoku Shinryokan (Okinawa, Japan)
  • Year and Date: 2012-10-29
• [Presentation] Structural basis of Atg8 activation by Atg7 (2011)
  • Author(s): Nobuo N. Noda
  • Organizer: 2nd Japan-Sino Autophagy Symposium
  • Place of Presentation: Shonan Village Center (Kanagawa, Japan)
  • Year and Date: 2011-10-07
• [Presentation] Structural basis of Atg8 activation and transfer to Atg3 by Atg7 (2011)
  • Author(s): Nobuo N. Noda
  • Organizer: Cold Spring Harbor Laboratory Meeting On The Ubiquitin Family
  • Place of Presentation: Cold Spring Harbor Laboratory (Cold Spring Harbor, USA)
  • Year and Date: 2011-05-19
• [Book] Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging Volume 3–Mitophagy (2014)
  • Author(s): Noda, N. N.他
  • Total Pages: 57-65
  • Publisher: Elsevier,Autophagy
• [Book] Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging Volume 2–Role in General Diseases (2013)
  • Author(s): Noda, N. N.他
  • Total Pages: 39-48
  • Publisher: Elsevier,Autophagy
• [Book] オートファジー生命をささえる細胞の自己分解システム (2013)
  • Author(s): 野田展生他
  • Total Pages: 77-88
  • Publisher: 化学同人
• [Book] Biochemistry (2011)
  • Author(s): Noda, N. N.他
  • Total Pages: 333-348
  • Publisher: InTECH
• [Book] Current Trends in X-Ray Crystallography (2011)
  • Author(s): Noda, N. N.他
  • Total Pages: 381-396
  • Publisher: InTECH
• [Remarks]
  • URL: http://www.bikaken.or.jp/laboratories/molecule/summary.html