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Single particle cryoEM of mammalian FoF1 ATP synthase

Research Project

Project/Area Number 17H03647
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

Gerle Christoph  大阪大学, 蛋白質研究所, 特任准教授(常勤) (10561970)

Co-Investigator(Kenkyū-buntansha) 森本 幸生  京都大学, 複合原子力科学研究所, 教授 (80200450)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Keywordsmitochondria / F-ATP synthase / cryo-EM / membrane protein / super complex / cristae / membrane architecture / membrane transport / supercomplex / protein structure / PTP / channel / 高分解能電子顕微鏡解析 / 膜タンパク質複合体 / クライオ電顕 / FoF1ATP合成酵素 / 膜蛋白質複合体 / FoF1ATP合成 / FoF1 ATP synthase / bioenergetics / single particle cryo-EM / structural biology / membrane biology / proton transport / rotary ATPase / 分子モータ / 蛋白質 / 電子顕微鏡 / 生体分子
Outline of Final Research Achievements

All the cells in our body rely on the sufficient and well balanced energy supply in the form of the molecule ATP. Most ATP is produced by a large membrane supercomplex, the F-ATP synthase. How this very large protein complex achieves its energy transformation function is not very well understood yet. In this project we attempted to improve our understanding by inventing novel ways to purify fragile F-ATP synthase from cow heart muscle tissue and analyze its structure and function by cryo electron microscopy and other methods. We succeeded to find new ways to purifiy the protein complex that preserves it during isolation. All physiological functions of the F-ATP synthase could be preserved. We also invented novel ways to put the F-ATP synthase into artificial membranes, which was important to confirm new channel functions of F-ATP synthase. In summary, we have now established a firm basis for structure and function analysis in solution as well as in artificial membrane systems.

Academic Significance and Societal Importance of the Research Achievements

哺乳類のF-ATP合成酵素は、ミトコンドリア疾患の鍵を握る存在として現在注目されている。今回のプロジェクトで得られた新しい調製法、膜の再構成、透過性遷移孔としての機能の発見は、F-ATP合成酵素の研究を前進させる上で重要な役割を果たすことが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (22 results)

All 2020 2019 2018 2017 Other

All Journal Article (6 results) (of which Int'l Joint Research: 6 results,  Open Access: 4 results,  Peer Reviewed: 5 results) Presentation (15 results) (of which Int'l Joint Research: 4 results,  Invited: 15 results) Remarks (1 results)

  • [Journal Article] The Dual Life of Mitochondrial F-ATP Synthase.2020

    • Author(s)
      Paolo, B., Szabo, I., Lippe, G., Gerle, C., and Forte, M.A.
    • Journal Title

      Biophysical Journal

      Volume: 118, 3 Issue: 3 Pages: 16a-16a

    • DOI

      10.1016/j.bpj.2019.11.270

    • Related Report
      2019 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Purified F-ATP synthase forms a Ca2+dependent high-conductance channel matching the mitochondrial permeability transition pore.2019

    • Author(s)
      Urbani A,Giorgio V,Carrer A, Franchin C,Arrigoni G, Jiko C,Abe K,Maeda S, Sginzawa-Itoh K, Bogers JF, McMillan DG, Gerle C, Szabo I, Bernardi P
    • Journal Title

      Nature communications

      Volume: 4341 Issue: 1 Pages: 4341-4341

    • DOI

      10.1038/s41467-019-12331-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Essay on Biomembrane Structure.2019

    • Author(s)
      Christoph Gerle
    • Journal Title

      Journal of Membrane Biology

      Volume: 252 Issue: 2-3 Pages: 115-130

    • DOI

      10.1007/s00232-019-00061-w

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The cristae modulator Optic atrophy 1 requires mitochondrial ATP synthase oligomers to safeguard mitochondrial function.2018

    • Author(s)
      Ruben Quintana-Cabrera, Charlotte Quirin, Christina Glytsou, Mauro Corrado, Andrea Urbani, Anna Pellattiero, Enrique Calvo, Jesus Vazquez, Jose; Antonio Enriquez, Christoph Gerle, Maria Eugenia Soriano, Paolo Bernardi & Luca Scorrano
    • Journal Title

      Nature communications

      Volume: 9 (3399) Issue: 1 Pages: 1-13

    • DOI

      10.1038/s41467-018-05655-x

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Protein assemblies ejected directly from native membranes yield complexes for mass spectrometry2018

    • Author(s)
      Dror S Chorev, Lindsay A Baker, Di Wu, Victoria Beilsten-Edmands, Sarah L Rouse, Tzviya Zeev-Ben-Mordehai, Chimari Jiko, Firdaus Samsudin, Christoph Gerle, Syma Khalid, Alastair G Stewart, Stephen J Matthews, Kay Grunewald, Carol V Robinson
    • Journal Title

      Science

      Volume: 362, 6416 Issue: 6416 Pages: 829-834

    • DOI

      10.1126/science.aau0976

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] RAZA: A Rapid 3D z-crossings algorithm to segment electron tomograms and extract organelles and macromolecules2017

    • Author(s)
      Ali Rubbiya A.、Mehdi Ahmed M.、Rothnagel Rosalba、Hamilton Nicholas A.、Gerle Christoph、Landsberg Michael J.、Hankamer Ben
    • Journal Title

      Journal of Structural Biology

      Volume: 200 Issue: 2 Pages: 73-86

    • DOI

      10.1016/j.jsb.2017.10.002

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] In and out of the membrane: cryo-EM of membrane proteins.2019

    • Author(s)
      Christoph Gerle
    • Organizer
      Asian Crystallographic Association
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Purified F-ATP synthase forms a Ca2+-dependent high-conductance channel matching the mitochondrial permeability transition pore.2019

    • Author(s)
      Christoph Gerle
    • Organizer
      Cold Spring Harbor Asia conference on Mitochondria
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mitochondrial F-ATP synthase: an old machine with new tricks.2019

    • Author(s)
      Christoph Gerle
    • Organizer
      Kluyver Colloquium, TU Delft, The Netherlands
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Membrane bending & more - in vitro studies of membrane protein supercomplexes.2019

    • Author(s)
      Christoph Gerle
    • Organizer
      Institute for Plant Biotechnology and Biology, University of Munster, Germany
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 牛心筋シトクロム-c酸化酵素 二量体か?単量体か?2018

    • Author(s)
      Christoph Gerle
    • Organizer
      日本生体エネルギー研究会第44回討論会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Membrane protein sample preparation for single-particle cryo-EM and more.2018

    • Author(s)
      Christoph Gerle
    • Organizer
      生理研研究会 「クライオ電子顕微鏡によるタンパク質の高分解能単粒子構造解析」~ これであなたも高分解能~
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Mammalian FoF1 ATP synthase as the mitochondrial permeability transition pore -? new drug targets in old proteins.2018

    • Author(s)
      Christoph Gerle
    • Organizer
      CeSPI Talk
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Cryo electron tomography of in vitro membrane systems.2018

    • Author(s)
      Christoph Gerle
    • Organizer
      KEK Symposium
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Is mammalian FoF1 ATP synthase the mitochondrial permeability transition pore?2018

    • Author(s)
      Christoph Gerle
    • Organizer
      EBEC
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Membrane bending and more - cryo-EM of integral membrane complexes.2018

    • Author(s)
      Christoph Gerle
    • Organizer
      Departmental Talk, Ruh University Bochum, Germany
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] GraDeR: detergent free membrane protein preparation.2018

    • Author(s)
      Christoph Gerle
    • Organizer
      Oxford Talks
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 哺乳動物F-ATP合成酵素はptp?2017

    • Author(s)
      Christoph Gerle
    • Organizer
      日本生体エネルギー研究会第43回討論会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Cryo-EM 2.02017

    • Author(s)
      Christoph Gerle
    • Organizer
      ConBio
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] The intermembrane space domain of mammalian FoF1 ATP synthase and its potential role in ptp formation.2017

    • Author(s)
      Christoph Gerle
    • Organizer
      Cold Spring Harbor Asia conference on Mitochondria
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] GraDeR: micelle free membrane protein preparation.2017

    • Author(s)
      Christoph Gerle
    • Organizer
      The 55th Annual Meeting of Biophysical Society of Japan
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Remarks] GraDeR

    • URL

      https://grader-protocol.com/

    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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