• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular basis of new protein quality control systems depending on the pH gradient between the ER and the Golgi

Research Project

Project/Area Number 15H04335
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionTohoku University

Principal Investigator

Inaba Kenji  東北大学, 多元物質科学研究所, 教授 (10423039)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2017: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywordsタンパク質品質管理 / 小胞体 / ゴルジ体 / X線結晶構造解析 / ERp44 / PDIファミリー / pH / 亜鉛 / 蛋白質 / 酵素 / PDI / 細胞 / X線結晶構造解析 / レドックス
Outline of Final Research Achievements

ERp44 is a PDI-family member protein that transports back ER-resident enzymes and immature secretory proteins from the Golgi to the ER and thereby conducts protein quality control in the early secretory pathway. In this reserach project, we succeeded in crystal structure analysis of ERp44 at pH7.5 and pH6.5. Based on the structural information, we performed a series of biochemical, biophysical and cell biological studies. Consequently, we revealed the molecular mechanism by which ERp44 regulates the substrate binding and release in a pH-dependent manner (Watanabe et al., PNAS 2017).

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (40 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (2 results) Journal Article (15 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 15 results,  Open Access: 8 results,  Acknowledgement Compliant: 4 results) Presentation (16 results) (of which Int'l Joint Research: 9 results,  Invited: 10 results) Book (2 results) Remarks (5 results)

  • [Int'l Joint Research] San Raffaele Scientific Institute(イタリア)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] San Raffaele Scientific Institute(Italy)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] The Highly Dynamic Nature of ERdj5 Is Key to Efficient Elimination of Aberrant Protein Oligomers through ER-Associated Degradation.2017

    • Author(s)
      Maegawa KI, Watanabe S#, Noi K#, Okumura M#, Amagai Y#, Inoue M, Ushioda R, Nagata K, Ogura T, Inaba K.(#equal contribution)
    • Journal Title

      Structure

      Volume: 25 Issue: 6 Pages: 846-857

    • DOI

      10.1016/j.str.2017.04.001

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preparation of Selenoinsulin as a Long-Lasting Insulin Analogue2017

    • Author(s)
      Kenta Arai+, Toshiki Takei+, Masaki Okumura+, Satoshi Watanabe+, Yuta Amagai, Yuya Asahina, Luis Moroder, Hironobu Hojo, Kenji Inaba, and Michio Iwaoka
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 印刷中 Issue: 20 Pages: 5522-5526

    • DOI

      10.1002/anie.201701654

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural basis of pH-dependent client binding by ERp44, a key regulator of protein secretion at the ER-Golgi interface.2017

    • Author(s)
      Watanabe, S., Harayama, M., Kanemura, S., Sitia, R. and Inaba, K.
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: in press Issue: 16 Pages: 3224-3232

    • DOI

      10.1073/pnas.1621426114

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics2017

    • Author(s)
      Akaike Takaaki、、、Nishida Motohiro(4)、、、、、、Fujii Shigemoto(20)、、、Motohashi Hozumi(26)
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 1177-1177

    • DOI

      10.1038/s41467-017-01311-y

    • NAID

      120007134656

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Preparation of selenoinsulin as a long-lasting insulin analog2017

    • Author(s)
      Arai, K.#, Takei, T.#, Okumura, M.#, Watanabe, S.#, Amagai, Y., Hojo, H.*, Inaba, K.* and Iwaoka, M.*
    • Journal Title

      Angewandte Chemie

      Volume: in press

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The highly dynamic nature of ERdj5 is key to efficient elimination of aberrant protein oligomers through ER-associated degradation2017

    • Author(s)
      Maegawa, K., Watanabe, S., Noi, K., Okumura, M., Amagai, Y., Inoue, M., Ushioda, R., Nagata, K., Ogura, T. and Inaba, K
    • Journal Title

      Structure

      Volume: in press

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Redox-assisted regulation of Ca2+ homeostasis in the endoplasmic reticulum by ERdj52016

    • Author(s)
      Ushioda, R., Miyamoto, A., Inoue, M., Watanabe, S., Okumura, M., Maegawa, K., Uegaki, K., Fujii, S., Fukuda, Y., Umitsu, M., Takagi, J., Inaba, K., Mikoshiba, K., Nagata, K.
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 113 Pages: 6055-6063

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human ER Oxidereductin-1a (Ero1a) undergoes dual regulation through complementary redox interactions with Protein Disulfide Isomerase.2016

    • Author(s)
      Kanemura, S., Okumura, M., Yutani, K., Ramming, T., Hikima, T., Appenzeller-Herzog, C., Akiyama, S., and Inaba, K.
    • Journal Title

      J. Biol. Chem.

      Volume: 291 Pages: 23952-23964

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The membrane topology of Vitamin K Epoxide Reductase is conserved between human isoforms and the bacterial enzyme2016

    • Author(s)
      Cao, Z, van Lith, M., Mitchell, L. J., Pringle, M. A., Inaba, K. and Bulleid, N. J.
    • Journal Title

      Biochem. J

      Volume: 473 Issue: 7 Pages: 851-858

    • DOI

      10.1042/bj20151223

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cysteines 208 and 241 in Ero1 are required for maximal catalytic turnover2015

    • Author(s)
      T. Ramming, S. Kanemura, M. Okumura, K. Inaba and C. Appenzeller-Herzog.
    • Journal Title

      Redox Biology

      Volume: 7 Pages: 14-20

    • DOI

      10.1016/j.redox.2015.11.004

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] One-dimensional sliding of p53 along DNA is accelerated in the presence of Ca(2+) or Mg(2+) at millimolar concentrations2015

    • Author(s)
      Murata A, Ito Y, Kashima R, Kanbayashi S, Nanatani K, Igarashi C, Okumura M, Inaba K, Tokino T, Takahashi S, Kamagata K
    • Journal Title

      JOURNAL OF MOLECULAR BIOLOGY

      Volume: 427 Issue: 16 Pages: 2663-2678

    • DOI

      10.1016/j.jmb.2015.06.016

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural basis of a Ni acquisition cycle for [NiFe]-hydrogenase by HypA and its enhancer.2015

    • Author(s)
      Watanabe, S., Kawashima, T., Nishitani, Y., Kanai, T., Wada, T., Inaba, K., Atomi, H., Imanaka, T. and Miki, K.
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 112 Issue: 25 Pages: 7701-7706

    • DOI

      10.1073/pnas.1503102112

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A PDI-catalyzed thiol/disulfide switch regulates the production of hydrogen peroxide by human Ero12015

    • Author(s)
      T. Ramming, M. Okumura, S. Kanemura, S. Baday, J. Birk, S. Moes, P. Jenö, S. Bernèche, K. Inaba and C. Appenzeller-Herzog.
    • Journal Title

      Free Radic Biol Med.

      Volume: 83 Pages: 361-372

    • DOI

      10.1016/j.freeradbiomed.2015.02.011

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structures and functions of protein disulfide isomerase family members involved in proteostasis in the endoplasmic reticulum.2015

    • Author(s)
      Okumura M, Kadokura H, Inaba K.
    • Journal Title

      Free Radic Biol Med.

      Volume: 83 Pages: 314-322

    • DOI

      10.1016/j.freeradbiomed.2015.02.010

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 新規PDIファミリータンパク質ERp46の構造と機能2015

    • Author(s)
      奥村 正樹、金村 進吾、稲葉 謙次
    • Journal Title

      日本生物物理学会会報誌

      Volume: 55 Pages: 34-36

    • NAID

      130004794735

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Presentation] The highly dynamic nature of ERdj5 plays a key role in efficient ER-associated degradation2018

    • Author(s)
      Inaba, K.
    • Organizer
      CLS Tokyo Tech. International Forum 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Structural and Mechanistic basis of pH- and Zn2+-dependent regulation of ERp44 for protein quality control in the early secretory pathway2017

    • Author(s)
      Inaba, K.
    • Organizer
      ER & Redox club meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] How do PDI family member proteins act on nascent chains to catalyze their oxidative protein2017

    • Author(s)
      奥村 正樹、平山 千尋、野井 健太郎、町田 幸大、今高 寛晃、小椋 光、稲葉 謙次
    • Organizer
      第17回日本蛋白質科学会年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Structural basis of redox-dependent regulation of Sarco/Endoplasmic reticulum Ca2+-ATPase 2b (SERCA2b)2017

    • Author(s)
      稲葉謙次
    • Organizer
      日本生物物理学会年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] システインの酸化還元を介した新たなタンパク質品質管理機構の構造基盤2017

    • Author(s)
      稲葉謙次
    • Organizer
      大阪大学蛋白質研究所セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Zn-dependent regulation of the protein quality control by ERp44 in the early secretory pathway2016

    • Author(s)
      Harayama, M., Watanabe, S., Amagai, Y., Sannino, S., Sitia, R., Inaba, K.
    • Organizer
      第39回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] 小胞体タンパク質品質管理に関与するERp44のpHと亜鉛イオンによる機能制御2016

    • Author(s)
      渡部 聡, 原山麻奈美, 天貝佑太, 増井翔史, Sara Sannino, Roberto Sitia, 稲葉謙次
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] How do PDI family member proteins act on unfolded/misfolded proteins to ensure protein quality control in the ER.2016

    • Author(s)
      Inaba, K.
    • Organizer
      Nascent chain biology meeting 2016
    • Place of Presentation
      富士レークホテル(山梨県河口湖町)
    • Year and Date
      2016-09-01
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Structural basis of pH- and zinc-dependent protein quality control by ERp442016

    • Author(s)
      Watanabe, S., Harayama, M., Amagai, Y., Sannino, S., Masui, S., Sitia, R. and Inaba, K.
    • Organizer
      Nascent chain biology meeting 2016
    • Place of Presentation
      富士レークホテル(山梨県河口湖町)
    • Year and Date
      2016-09-01
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 亜鉛イオンによるERp44を介した小胞体タンパク質品質管理機構の分子基盤2016

    • Author(s)
      渡部 聡, 原山麻奈美, 天貝佑太, 増井翔史, Sara Sannino, Roberto Sitia, 稲葉謙次
    • Organizer
      第16回日本蛋白質科学会年会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-06-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] Dynamic natures of PDI family members in catalysis of oxidative protein folding and ER associated degradation2015

    • Author(s)
      Inaba, K
    • Organizer
      Symposium: From cytosol to ER; Translation, translocation and modification
    • Place of Presentation
      東北大学片平キャンパス生命科学研究科プロジェクト棟(仙台市)
    • Year and Date
      2015-11-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Dynamic natures of PDI family member proteins that act on nascent chains in the endoplasmic reticulum2015

    • Author(s)
      Inaba, K
    • Organizer
      Nascent chain biology meeting
    • Place of Presentation
      東京大学本郷キャンパス一条ホール(東京)
    • Year and Date
      2015-10-01
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Real-time monitoring of PDI-catalyzed oxidative protein folding by high-speed atomic force microscopy2015

    • Author(s)
      奥村正樹、野井健太郎,金村進吾、増井翔史、引間孝明、秋山修志、小椋光、稲葉謙次
    • Organizer
      第53回 生物物理学会年会
    • Place of Presentation
      金沢大学角間キャンパス自然科学本館(金沢市)
    • Year and Date
      2015-09-13
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Dynamic natures of PDI family members in catalysis of oxidative protein folding and ER associated degradation2015

    • Author(s)
      Inaba, K
    • Organizer
      EMBO meeting
    • Place of Presentation
      Birmingham, UK
    • Year and Date
      2015-09-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Dynamic natures of PDI family members in catalysis of oxidative protein folding and ER associated degradation2015

    • Author(s)
      Inaba, K
    • Organizer
      Case Western Reserve University-Tohoku University joint symposium
    • Place of Presentation
      Cleaveland, USA
    • Year and Date
      2015-07-29
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Dual conformations of ERdj5 play a significant role in acceleration of the ER associated degradation.2015

    • Author(s)
      Inaba, K
    • Organizer
      ER & Redox club meeting
    • Place of Presentation
      Venice, Italy
    • Year and Date
      2015-04-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Book] Oxidative folding of Peptides and Proteins2018

    • Author(s)
      M. Okumura, S. Watanabe, and K. Inaba
    • Publisher
      Royal Society of Chemistry
    • Related Report
      2017 Annual Research Report
  • [Book] 分子研レターズ2017

    • Author(s)
      金村 進吾、奥村 正樹、稲葉 謙次
    • Publisher
      分子研
    • Related Report
      2017 Annual Research Report
  • [Remarks] 東北大学多元物質科学研究所生体分子構造研究分野 稲葉研究室

    • URL

      http://www.tagen.tohoku.ac.jp/labo/inaba/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 東北大学 多元物質科学研究所 生体分子構造研究分野 稲葉研究室

    • URL

      http://www.tagen.tohoku.ac.jp/labo/inaba/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 細胞内pH変化を利用したタンパク質品質管理のメカニズム ‐pHセンシング機構の構造基盤を解明‐

    • URL

      http://www2.tagen.tohoku.ac.jp/lab/news_press/20170404/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 東北大学生命科学研究科分子生命科学専攻 稲葉謙次

    • URL

      http://www.lifesci.tohoku.ac.jp/teacher/t_inaba/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 東北大学多元物質科学研究所 生体分子構造研究分野ホームページ

    • URL

      http://www.tagen.tohoku.ac.jp/labo/inaba/

    • Related Report
      2015 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi