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Development of technical basis for direct observations of membrane protein complex in dynamic equilibrium under a physiological condition

Research Project

Project/Area Number 15K15035
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General physiology
Research InstitutionKeio University

Principal Investigator

SOHMA Yoshiro  慶應義塾大学, 医学部(信濃町), 准教授 (60268183)

Co-Investigator(Renkei-kenkyūsha) UCHIHASHI Takayuki  金沢大学, 数物科学系, 准教授 (30326300)
NISHIZAKA Takayuki  学習院大学, 理学部, 教授 (40359112)
SAKURAI Minoru  東京工業大学, バイオ研究基盤支援総合センター, 教授 (50162342)
SATO Chikara  独立行政法人産業技術総合研究所, バイオメディカル研究部門, 研究グループ長 (00357146)
Research Collaborator YU Ying-Chun  
HWANG Tzyh-Chang  
KATO Takanobu  
FUJIMURA Shoko  
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords分子間相互作用 / 高速原子間力顕微鏡 / 1分子直接観察 / 膜蛋白複合体 / 脂質2重膜 / ラフト / 抗原ー抗体反応 / アクアポリン
Outline of Final Research Achievements

Membrane proteins functions with forming a complex in the plasma membrane. The mechanism of the membrane protein complexes is one of the most important in the physiology and medicine. We attempted to develop the technical basis for the direct observation of membrane protein complexes working in non-equilibrium dynamics under a physiological condition using the high-speed atomic force microscopy (HS-AFM).
We found that the ‘Nanodisc’ should be the most likely candidate for the central parts of the ‘physiological AFM platform’ allowing us the successful direct observation for ‘in vivo’-like dynamics of membrane protein complexes. We also attempted to establish a fundamental theory for interpreting the HS-AFM movie data of the intermolecular interaction. Several issues appeared in the theoretical study suggested the existence of an unknown important process for the intermolecular interaction in a mesoscopic level between the single-molecular and the macroscopic levels

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (16 results)

All 2017 2016 2015 Other

All Int'l Joint Research (2 results) Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 3 results) Presentation (8 results) (of which Int'l Joint Research: 2 results) Remarks (3 results)

  • [Int'l Joint Research] DCRC, Univ of Missouri - Columbia(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] University of Missouri-Columbia(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Bicarbonate-rich fluid secretion predicted by a computational model of guinea-pig pancreatic duct epithelium.2017

    • Author(s)
      Yamaguchi M, Steward MC, Smallbone K, Sohma Y, Yamamoto A, Ko SBH, Kondo T, Ishiguro H
    • Journal Title

      Journal of Physiology

      Volume: 595 Issue: 6 Pages: 1947-1972

    • DOI

      10.1113/jp273306

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Synergistic Potentiation of Cystic Fibrosis Transmembrane Conductance Regulator Gating by Two Chemically Distinct Potentiators, Ivacaftor (VX-770) and 5-Nitro-2-(3-Phenylpropylamino) Benzoate.2016

    • Author(s)
      Lin WY, Sohma Y, Hwang TC
    • Journal Title

      Molecular Pharmacology

      Volume: 90 Issue: 3 Pages: 275-285

    • DOI

      10.1124/mol.116.104570

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] On the mechanism of gating defects caused by the R117H mutation in CFTR.2016

    • Author(s)
      Yu YC, Sohma Y, Hwang TC
    • Journal Title

      The Journal of Physiology

      Volume: 000.0 Issue: 12 Pages: 1-18

    • DOI

      10.1113/jp271723

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Characterization of a CFTR-mutant frequently found in Japanese cystic fibrosis patients.2017

    • Author(s)
      Nakao K, Nakakuki M, Ishiguro H, Sohma Y
    • Organizer
      14th Eeuropean Cystic Fibrosis Society Basic Science Conference
    • Place of Presentation
      Algarve, Portugal
    • Year and Date
      2017-03-29
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 嚢胞性線維症日本人患者から同定された変異型CFTRの特性解析2017

    • Author(s)
      中尾香菜子、石倉麗音奈、中莖みゆき、石黒 洋、政池知子、相馬義郎
    • Organizer
      第94回日本生理学会年会
    • Place of Presentation
      アクトシティ浜松(静岡県浜松市)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] 日本人嚢胞性線維症患者から同定されたCFTR変異体の解析2017

    • Author(s)
      中尾香菜子、石倉麗音奈、中莖みゆき、安井正人、石黒 洋、政池知子、相馬義郎
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール(長崎県長崎市)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] CFTR and AQP: Two channels deeply involved into incurable diseases2016

    • Author(s)
      相馬義郎
    • Organizer
      第93回日本生理学会年会シンポジウム
    • Place of Presentation
      札幌コンベンションセンター、札幌
    • Year and Date
      2016-03-22
    • Related Report
      2015 Research-status Report
  • [Presentation] Dynamic Bindings of Autoimmune IgG Antibodies against Autoantigen Membrane Proteins directly Observed by High-Speed Atomic Force Microscopy (HS-AFM)2015

    • Author(s)
      Sohma Y
    • Organizer
      TheSecond Kitasato-Yale Fluid Symposium: Molecular Control of Cellular and Epithelial Function
    • Place of Presentation
      北里大学、白金、東京
    • Year and Date
      2015-12-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 高速原子間力顕微鏡を用いた 水チャネル AQP4 への 自己抗体の 結合・解離動態の直接観察2015

    • Author(s)
      相馬義郎、山下隼人
    • Organizer
      平成27年度生理学研究所研究会「生体ホメオスタシスのgatewayとしての上皮膜輸送マイクロホメオスタシス
    • Place of Presentation
      生理学研究所、岡崎
    • Year and Date
      2015-09-15
    • Related Report
      2015 Research-status Report
  • [Presentation] Monitoring ATP-hydrolysis cycle by electro-physiological approach: Patch-clamp recordings of CFTR2015

    • Author(s)
      相馬義郎
    • Organizer
      第53回日本生物物理学会年会シンポジウム
    • Place of Presentation
      金沢大学、金沢
    • Year and Date
      2015-09-13
    • Related Report
      2015 Research-status Report
  • [Presentation] 高速原子間力顕微鏡を用いた膜蛋白への抗体結合・解離動態の直接観察2015

    • Author(s)
      相馬義郎、山下隼人
    • Organizer
      平成27年度生理学研究所研究会「膜システムの機能的・構造的統合」
    • Place of Presentation
      生理学研究所、岡崎
    • Year and Date
      2015-09-01
    • Related Report
      2015 Research-status Report
  • [Remarks] 慶應義塾大学医学部薬理学教室教員紹介

    • URL

      http://www.pharm.med.keio.ac.jp/about/sohma.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 相馬 義郎 - 慶應義塾大学医学部薬理学教室 - Keio University

    • URL

      http://www.pharm.med.keio.ac.jp/about/sohma.html

    • Related Report
      2015 Research-status Report
  • [Remarks] Yoshiro Sohma - DCRC UMC

    • URL

      http://dalton.missouri.edu/investigators/sohmay.php

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2022-02-16  

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