Structural basis of Atg proteins responsible for autophagy

• Project Area: Multidisciplinary research on autophagy: from molecular mechanisms to disease states
• Project/Area Number: 25111004
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• 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, 部長 (40396297)
• Project Period (FY): 2013-06-28 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥126,490,000 (Direct Cost: ¥97,300,000、Indirect Cost: ¥29,190,000); Fiscal Year 2017: ¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000); Fiscal Year 2016: ¥23,790,000 (Direct Cost: ¥18,300,000、Indirect Cost: ¥5,490,000); Fiscal Year 2015: ¥24,570,000 (Direct Cost: ¥18,900,000、Indirect Cost: ¥5,670,000); Fiscal Year 2014: ¥22,880,000 (Direct Cost: ¥17,600,000、Indirect Cost: ¥5,280,000); Fiscal Year 2013: ¥35,230,000 (Direct Cost: ¥27,100,000、Indirect Cost: ¥8,130,000)
• Keywords: オートファジー / 結晶構造 / リン酸化 / 選択的オートファジー / 構造生物学 / 高次会合体 / Atg101 / Atg8 / Atg1複合体 / Atg13 / Atg17 / 飢餓応答

Outline of Final Research Achievements

We have determined the crystal structures of the autophagy-initiating Atg1 complex and Atg101, the worm homologs of Atg8 that mediate autophagosome formation and cargo recognition, as well as the selective cargo Ape1 and its adaptor Atg19. By functional analyses based on the structural information, we have revealed the molecular mechanisms of autophagy initiation upon starvation, different functions mediated by Atg8 homologs, and selective recognition of protein aggregates during selective autophagy.

Research Products

• [Int'l Joint Research] NIBS(China)
• [Int'l Joint Research] NINDS(米国)
• [Int'l Joint Research] Chinese Academy of Sciences/Nankai University/Anhui Medical University(China)
• [Journal Article] Atg7 Activates an Autophagy-Essential Ubiquitin-like Protein Atg8 through Multi-Step Recognition (2018)
  • Author(s): Yamaguchi Masaya、Satoo Kenji、Suzuki Hironori、Fujioka Yuko、Ohsumi Yoshinori、Inagaki Fuyuhiko、Noda Nobuo N.
  • Journal Title: Journal of Molecular Biology Volume: 430 Issue: 3 Pages: 249-257
  • DOI: 10.1016/j.jmb.2017.12.002
  • Peer Reviewed
• [Journal Article] Endosomal Rab cycles regulate Parkin-mediated mitophagy. (2018)
  • Author(s): Yamano K, Wang C, Sarraf SA, Münch C, Kikuchi R, Noda NN, Hizukuri Y, Kanemaki MT, Harper W, Tanaka K, Matsuda N, Youle RJ.
  • Journal Title: eLife Volume: 7
  • DOI: 10.7554/elife.31326
  • NAID: 120006457172
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] オートファジーを制御するタンパク質群の構造と機能 (2018)
  • Author(s): 野田 展生
  • Journal Title: バイオサイエンスとインダストリー Volume: 76 Pages: 12-19
  • NAID: 40021446305
• [Journal Article] Autophagy-regulating protease Atg4: structure, function, regulation and inhibition. (2017)
  • Author(s): Maruyama, T. and *Noda, N. N.
  • Journal Title: The Journal of Antibiotics Volume: 71 Issue: 1 Pages: 72-78
  • DOI: 10.1038/ja.2017.104
  • Peer Reviewed / Open Access
• [Journal Article] Biophysical characterization of Atg11, a scaffold protein essential for selective autophagy in yeast (2017)
  • Author(s): Suzuki, H. and *Noda, N. N.
  • Journal Title: FEBS Open Bio Volume: 8 Issue: 1 Pages: 110-116
  • DOI: 10.1002/2211-5463.12355
  • Peer Reviewed / Open Access
• [Journal Article] オートファジーの始動機構を観る (2017)
  • Author(s): 野田 展生
  • Journal Title: 医学のあゆみ Volume: 262 Pages: 373-378
• [Journal Article] Structural biology of the Cvt pathway (2017)
  • Author(s): Yamasaki A, Noda NN
  • Journal Title: Journal of Molecular Biology Volume: 429 Issue: 4 Pages: 531-542
  • DOI: 10.1016/j.jmb.2017.01.003
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Structural biology of the core autophagy machinery. (2017)
  • Author(s): Suzuki H, Osawa T, Fujioka Y, Noda NN
  • Journal Title: Current Opinion in Structural Biology Volume: 43 Pages: 10-17
  • DOI: 10.1016/j.sbi.2016.09.010
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The Intrinsically Disordered Protein Atg13 Mediates Supramolecular Assembly of Autophagy Initiation Complexes. (2016)
  • Author(s): Yamamoto H, Fujioka Y, Suzuki SW, Noshiro D, Suzuki H, Kondo-Kakuta C, Kimura Y, Hirano H, Ando T, Noda NN, Ohsumi Y
  • Journal Title: Developmental Cell Volume: 38 Issue: 1 Pages: 86-99
  • DOI: 10.1016/j.devcel.2016.06.015
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Structural mechanisms of receptor-mediated selective autophagy of aggregated aminopeptidase I. (2016)
  • Author(s): Akinori Yamasaki, Yasunori Watanabe, Wakana Adachi, Kuninori Suzuki, Kazuaki Matoba, Hiromi Kirisako, Hiroyuki Kumeta, Hitoshi Nakatogawa, Yoshinori Ohsumi, Fuyuhiko Inagaki and Nobuo N. Noda
  • Journal Title: Cell Reports Volume: 16 Issue: 1 Pages: 19-27
  • DOI: 10.1016/j.celrep.2016.05.066
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Atg101: Not Just an Accessory Subunit in the Autophagy-initiation Complex (2016)
  • Author(s): Noda, N.N., Mizushima, N.
  • Journal Title: Cell Structure and Function Volume: 41 Issue: 1 Pages: 13-20
  • DOI: 10.1247/csf.15013
  • NAID: 130005126756
  • ISSN: 0386-7196, 1347-3700
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Small differences make a big impact: Structural insights into the differential function of the 2 Atg8 homologs in C. elegans. (2016)
  • Author(s): Wu, F., Wang, P., Shen, Y., Noda, N. N., Zhang, H.
  • Journal Title: Autophagy Volume: 12 Issue: 3 Pages: 606-607
  • DOI: 10.1080/15548627.2015.1137413
  • Int'l Joint Research
• [Journal Article] Structure of the Atg101-Atg13 complex reveals essential roles of Atg101 in mammalian autophagy initiation. (2015)
  • Author(s): Suzuki, H., Kaizuka, T., Mizushima, N., Noda, N. N.
  • Journal Title: Nature Structural & Molecular Biology Volume: 22 Issue: 7 Pages: 572-580
  • DOI: 10.1038/nsmb.3036
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Structural basis of the differential function of the two C. elegans Atg8 homologs, LGG-1 and LGG-2, in autophagy. (2015)
  • Author(s): Wu, F., Watanabe, Y., Guo, X. Y., Qi, X., Wang, P., Zhao, H. Y., Wang, Z., Fujioka, Y., Zhang, H., Ren, J. Q., Fang, T. C., Shen, Y. X., Feng, W., Hu, J. J., Noda, N. N., Zhang, H.
  • Journal Title: Molecular Cell Volume: 60 Issue: 6 Pages: 914-929
  • DOI: 10.1016/j.molcel.2015.11.019
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The thermotolerant yeast Kluyveromyces marxianus is a useful organism for structural and biochemical studies of autophagy. (2015)
  • Author(s): Yamamoto, H., Shima, T., Yamaguchi, M., Mochizuki, Y., Hoshida, H., Kakuta, S., Kondo-Kakuta, C., Noda, N. N., Inagaki, F., Itoh, T., Akada, R., Ohsumi, Y.
  • Journal Title: The Journal of Biological Chemistry Volume: 290 Issue: 49 Pages: 29506-29518
  • DOI: 10.1074/jbc.m115.684233
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mechanisms of autophagy (2015)
  • Author(s): Noda, N. N., Inagaki, F.
  • Journal Title: Annual Review of Biophysics Volume: 44 Issue: 1 Pages: 101-122
  • DOI: 10.1146/annurev-biophys-060414-034248
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Atg1 family kinases in autophagy initiation. (2015)
  • Author(s): Noda, N. N., Fujioka, Y.
  • Journal Title: Cellular and Molecular Life Sciences Volume: 72 Issue: 16 Pages: 3083-3096
  • DOI: 10.1007/s00018-015-1917-z
  • Peer Reviewed / Open Access
• [Journal Article] Open and closed HORMAs regulate autophagy initiation. (2015)
  • Author(s): Suzuki, H., Kaizuka, T., Mizushima, N., Noda, N.N.
  • Journal Title: Autophagy Volume: 11 Issue: 11 Pages: 2123-2124
  • DOI: 10.1080/15548627.2015.1091144
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Structural Basis of Starvation-induced Assembly of the Autophagy Initiation Complex (2015)
  • Author(s): 藤岡優子、野田展生
  • Journal Title: Nihon Kessho Gakkaishi Volume: 57 Issue: 3 Pages: 191-197
  • DOI: 10.5940/jcrsj.57.191
  • NAID: 130005085906
  • ISSN: 0369-4585, 1884-5576
  • Peer Reviewed / Open Access
• [Journal Article] Structure and Function of Atg101-Atg13 HORMA Heterodimer: Insight into Mammalian Autophagy Initiation (2015)
  • Author(s): 鈴木浩典、野田展生
  • Journal Title: Nihon Kessho Gakkaishi Volume: 57 Issue: 6 Pages: 324-330
  • DOI: 10.5940/jcrsj.57.324
  • NAID: 130005115747
  • ISSN: 0369-4585, 1884-5576
  • Peer Reviewed / Open Access
• [Journal Article] Structural basis of starvation-induced assembly of the autophagy initiation complex (2014)
  • Author(s): Yuko Fujioka, Sho W Suzuki, Hayashi Yamamoto, Chika Kondo-Kakuta, Yayoi Kimura, Hisashi Hirano, Rinji Akada, Fuyuhiko Inagaki, Yoshinori Ohsumi, Nobuo N Noda
  • Journal Title: NATURE STRUCTURAL & MOLECUIAR BIOLOGY Volume: 21(発表確定) Issue: 6 Pages: 513-521
  • DOI: 10.1038/nsmb.2822
  • Peer Reviewed
• [Journal Article] オートファゴソームの形成にかかわるタンパク質の構造と分子機能 (2014)
  • Author(s): 野田展生，稲垣冬彦
  • Journal Title: 領域融合レビュー Volume: 3
  • Peer Reviewed / Open Access
• [Journal Article] オートファジーの作動機構 (2014)
  • Author(s): 野田展生、稲垣冬彦
  • Journal Title: 実験医学 Volume: 32 Pages: 1612-1616
• [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: 85 Pages: 762-774
  • NAID: 10031202188
• [Presentation] オートファジー初期過程の試験管内再構成 (2018)
  • Author(s): 野田 展生
  • Organizer: 大阪大学蛋白質研究所セミナー
  • Invited
• [Presentation] 構造生物学から迫るオートファジーの分子機構 (2017)
  • Author(s): 野田展生
  • Organizer: 2016年度量子ビームサイエンスフェスタ
  • Place of Presentation: つくば国際会議場，茨城県つくば市
  • Year and Date: 2017-03-14
  • Invited
• [Presentation] 構造生物学から迫るオートファジーの分子機構 (2017)
  • Author(s): 野田 展生
  • Organizer: 平成29年度第１回構造生物学研究会
  • Invited
• [Presentation] 天然変性タンパク質Atg13 によるオートファジー始動の制御機構 (2017)
  • Author(s): 野田 展生
  • Organizer: 第17 回日本蛋白質科学会年会
  • Invited
• [Presentation] Identification of helical AIMs as a novel type of Atg8-interacting motif. (2017)
  • Author(s): Nobuo N. Noda
  • Organizer: The 8th International Symposium on Autophagy
  • Int'l Joint Research / Invited
• [Presentation] NMRとX線結晶解析の協業から迫るオートファジーの分子機構 (2016)
  • Author(s): 野田展生，稲垣冬彦
  • Organizer: 第55回NMR討論会
  • Place of Presentation: 広島国際会議場，広島県広島市
  • Year and Date: 2016-11-18
  • Invited
• [Presentation] Atg1複合体の動的構造解析 (2016)
  • Author(s): 野田展生
  • Organizer: 第10回オートファジー研究会
  • Place of Presentation: NASPA ニューオータニ，新潟県越後湯沢市
  • Year and Date: 2016-11-15
  • Invited
• [Presentation] Structural insights into autophagy machineries (2016)
  • Author(s): 野田展生
  • Organizer: リエゾンラボ研究会
  • Place of Presentation: 熊本大学発生医学研究所，熊本県熊本市
  • Year and Date: 2016-11-02
  • Invited
• [Presentation] オートファジー始動複合体の構造基盤 (2016)
  • Author(s): 野田展生
  • Organizer: 第68回日本細胞生物学会大会
  • Place of Presentation: 京都テルサ，京都府京都市
  • Year and Date: 2016-06-17
  • Invited
• [Presentation] オートファジーの構造生物学的研究 (2016)
  • Author(s): 野田展生
  • Organizer: 第58回構造生物応用研究会
  • Place of Presentation: 東京大学山上会館，東京都文京区
  • Year and Date: 2016-06-01
  • Invited
• [Presentation] Structural basis of the Cvt pathway (2016)
  • Author(s): Nobuo N. Noda
  • Organizer: The 4th Sino-Japan Symposium on Autophagy
  • Place of Presentation: Chinese Academy of Science, Beijing, China
  • Year and Date: 2016-04-23
  • Int'l Joint Research / Invited
• [Presentation] Structural basis of the autophagy initiating PAS assembly. (2016)
  • Author(s): Nobuo N. Noda
  • Organizer: Gordon Research Conference: Autophagy in Stress, Development & Disease
  • Place of Presentation: Ventura Beach Marriott, Ventura, CA, USA
  • Year and Date: 2016-03-22
  • Int'l Joint Research
• [Presentation] 選択的オートファジーの構造生物学的研究 (2015)
  • Author(s): 野田展生
  • Organizer: 第9回オートファジー研究会
  • Place of Presentation: 淡路夢舞台，兵庫県淡路市
  • Year and Date: 2015-11-16
  • Invited
• [Presentation] オートファジーの始動を担うAtg1/ULK複合体の構造と機能 (2015)
  • Author(s): 野田展生
  • Organizer: 第53回 日本生物物理学会年会
  • Place of Presentation: 金沢大学角間キャンパス，石川県金沢市
  • Year and Date: 2015-09-15
  • Invited
• [Presentation] オートファジーによる選択的蛋白質分解の構造基盤 (2015)
  • Author(s): 野田展生
  • Organizer: 第15回日本蛋白質科学会年会
  • Place of Presentation: あわぎんホール，徳島県徳島市
  • Year and Date: 2015-06-24
  • Invited
• [Presentation] Structural basis of the autophagy-initiating Atg1 complex (2015)
  • Author(s): Fujioka, Y., Suzuki, S. W., Yamamoto, H., Kimura, Y., Hirano, H., Ohsumi, Y., Noda, N. N.
  • Organizer: The 7th International Symposium on Autophagy
  • Place of Presentation: Smoky Willow, Huangshan, China
  • Year and Date: 2015-03-23
• [Presentation] Structure and regulation of the autophagy initiation complex. (2014)
  • Author(s): Noda, N. N.
  • Organizer: The 16th Northeastern Asian Symposium on Autophagy: from Basic to Medicine
  • Place of Presentation: Westin Chosun Hotel Busan, Korea
  • Year and Date: 2014-12-19
  • Invited
• [Presentation] Atg1複合体の構造基盤 (2014)
  • Author(s): 野田展生
  • Organizer: 第8回オートファジー研究会
  • Place of Presentation: ガトーキングダムサッポロ，北海道札幌市
  • Year and Date: 2014-11-10
  • Invited
• [Presentation] Structural insights into ubiquitin-like modifications essential for autophagy (2014)
  • Author(s): Noda, N. N.
  • Organizer: 23rd Congress and General Assembly of the International Union of Crystallography
  • Place of Presentation: Palais des congres de Montreal, Montreal, Canada
  • Year and Date: 2014-08-07
  • Invited
• [Presentation] Structural basis of autophagy initiation by starvation (2014)
  • Author(s): Fujioka, Y., Suzuki, S. W., Yamamoto, H., Kondo-Kakuta, C., Kimura, Y., Hirano, H., Akada, R., Inagaki, F., Ohsumi, Y., Noda, N. N.
  • Organizer: The 4th Asia Pacific Protein Association Conference
  • Place of Presentation: ICC JEJU, Jeju Island, Korea
  • Year and Date: 2014-05-18
  • Invited
• [Presentation] オートファゴソームの形成と選択的積荷取り込みの構造基盤
  • Author(s): 野田 展生
  • Organizer: 第８６回日本生化学会大会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Invited
• [Presentation] 飢餓によるオートファジー始動の分子機構
  • Author(s): 野田 展生
  • Organizer: 細胞内ロジスティクスシンポジウム
  • Place of Presentation: 淡路夢舞台国際会議場（兵庫県淡路市）
  • Invited
• [Presentation] Structural basis of autophagy initiation by starvation.
  • Author(s): Nobuo N. Noda
  • Organizer: 3rd China-Japan Symposium on Autophagy
  • Place of Presentation: 敦煌国際ホテル（敦煌，中国）
  • Invited
• [Presentation] 飢餓によるオートファジー始動の分子機構
  • Author(s): 野田 展生
  • Organizer: 第7回オートファジー研究会
  • Place of Presentation: ヤマハリゾートつま恋（静岡県掛川市）
  • Invited
• [Remarks] 微生物化学研究所構造生物学研究部
  • URL: http://www.bikaken.or.jp/laboratories/structuralbiology/summary.html
• [Remarks] 微生物化学研究所 論文一覧
  • URL: http://www.bikaken.or.jp/research/publications/index.php
• [Remarks] 公益財団法人微生物化学研究会微生物化学研究所分子構造解析部
  • URL: http://www.bikaken.or.jp/laboratories/molecule/summary.html