Study for ATP-driven transport mechanism of ABC transporters based on the "ATP hydrolysis switch" hypothesis.

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590212
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General physiology
• Research Institution: Keio University
• Principal Investigator: SOHMA Yoshiro 慶應義塾大学, 医学部, 准教授 (60268183)
• Co-Investigator(Kenkyū-buntansha): HAYASHI Mariko 慶應義塾大学, 医学部, 助教 (30525811)
• Co-Investigator(Renkei-kenkyūsha): SATO Chikara 独立行政法人産業技術総合研究所, 脳神情報研究部門, 研究グループ長 (00357146) ; 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) ; YASUI Masato 慶應義塾大学, 医学部, 教授 (90246637)
• Project Period (FY): 2010 – 2012
• Keywords: 生体膜 / チャネル / トランスポーター / 能動輸送

Research Abstract

Investigating the ATP-dependent gating kinetics of CFTR channel, a member of ABC transporter superfamily in detail revealed a loose coupling between ATP-hydrolysis cycle (chemical energy generated) and the pore gating cycle (mechanical energy consumed) as

Research Products

• [Journal Article] The power stroke driven by ATP binding in CFTR as studied by molecular dynamics simulations. (2013)
  • Author(s): Furukawa-Hagiya T, Furuta T, Chiba S, Sohma Y, Sakurai M
  • Journal Title: J. Phys. Chem. B Volume: 117 Pages: 3- 93
  • DOI: doi:10.1021/jp308315w
  • Peer Reviewed
• [Journal Article] Non-integral stoichiometry in CFTR gating revealed by a pore-lining mutation (2012)
  • Author(s): Jih KY, Sohma Y, Hwang TC
  • Journal Title: J. Gen. Physiol Volume: 140 Pages: 347 - 359
  • DOI: doi:10.1085/jgp.201210834
  • Peer Reviewed
• [Journal Article] Identification of a novel post-hydrolytic state in CFTR gating (2012)
  • Author(s): Jih KY, Sohma Y, Li M, Hwang TC
  • Journal Title: J. Gen. Physiol. Volume: 139 Pages: 359 - 370
  • DOI: doi:10.1085/jgp.201210789
  • Peer Reviewed
• [Journal Article] Curcumin and genistein additively potentiate G551D-CFTR. (2011)
  • Author(s): Yu YC, Miki H, Nakamura Y, Hanyuda A, Matsuzaki Y, Abe Y, Yasui M, Tanaka K, Hwang TC, Bompadre SB, Sohma Y.
  • Journal Title: J. Cystic Fibrosis Volume: 10 Pages: 243 - 252
  • DOI: doi:10.1016/j.jcf.2011.03.001
  • Peer Reviewed
• [Journal Article] On the mechanism of CFTR inhibition by a thiazolidinone derivative. (2010)
  • Author(s): Kopeikin Z, Sohma Y, Li M, Hwang TC
  • Journal Title: J. Gen. Physiol. Volume: 136 Pages: 659- 671
  • DOI: doi:10.1085/jgp.201010518
  • Peer Reviewed
• [Journal Article] A stable ATP binding to nucleotide binding domain is important for reliable gating cycle in an ABC transporter CFTR (2010)
  • Author(s): Shimizu H, Yu YC, Kono K, Kubota T, Yasui M, Li M, Hwang TC, Sohma Y
  • Journal Title: J. Physiol. Sci Volume: 60 Pages: 353 - 362
  • DOI: doi:10.1007/s12576-010-0102-2
  • Peer Reviewed
• [Presentation] 高速AFMによるCFTRチャネルのゆらぎの一分子動態観察 (2013)
  • Author(s): 相馬義郎
  • Organizer: 第90回日本生理学会年会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 20130327-29
• [Presentation] 高速AFM によるCFTR チャネルの動態観察 (2012)
  • Author(s): Yamashita H, Mio K, Mio M, Uchihashi T, Yasui M, Ando T, Sohma Y
  • Organizer: 第50回日本生物物理学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 20120922-24
• [Presentation] ABCトランスポータCFTRチャネルのATP加水分解駆動性ゲーティングの構造機能連関 (2012)
  • Author(s): 相馬 義郎
  • Organizer: 第89回日本生理学会年会 シンポジウム
  • Place of Presentation: 松本
  • Year and Date: 20120329-31
• [Presentation] Effects of genistein and curcumin on non-hydrolytic CFTR mutants (2012)
  • Author(s): Nakamura Y, Hanyuda A, Yu YC, Hagiya-Furukawa T, Odera M, Hwang TC, Sakurai M, Yasui M, Sohma Y.
  • Organizer: 56th Biophysical Society Annual Meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 20120225-29
• [Presentation] ABCトランスポータCFTRチャネルのATP駆動性ゲーティング:静止画から動画へ (2012)
  • Author(s): 相馬 義郎
  • Organizer: 第85回日本薬理学会年会シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2012-03-14
• [Presentation] ABCトランスポータ・CFTRチャネルにおけるATP加水分解の成否を決めている作動サイクル中間状態 (2011)
  • Author(s): 余 盈君, 古川(萩谷) 朋佳, 安井 正人, Hwang TC, 櫻井 実, 相馬 義郎
  • Organizer: 第49回日本生物物理学会年会
  • Place of Presentation: 姫路
  • Year and Date: 20110916-18
• [Presentation] A hidden intermediate state for priming ATP-hydrolysis during open conformation in CFTR channels (2011)
  • Author(s): Sohma Y, Yu YC, Yasui M, Hwang TC.
  • Organizer: 55th Biophysical Society Annual Meeting
  • Place of Presentation: Baltimore, Maryland, USA
  • Year and Date: 20110305-09
• [Presentation] A hidden open state for priming ATP-hydrolysis in an ABC transporter CFTR channel. (2011)
  • Author(s): Yu YC, Furukawa-Hagiya T, Nakamura Y, Yasui M, Hwang TC, Sakurai M, Sohma Y.
  • Organizer: 第88回 日本生理学会年会
  • Place of Presentation: Journal of Physiological Sciences 誌上開催
  • Year and Date: 20110300
• [Presentation] Two possible mechanisms underlying a halt of NBD gating engine induced by instability of ATP binding in an ABC transporter CFTR. (2010)
  • Author(s): Yu YC, Sohma Y, Hwang TC, Yasui M.
  • Organizer: 第48回 日本生物物理学会年会
  • Place of Presentation: 仙台
  • Year and Date: 20100920-22
• [Book] Pharmaceutical implications of curcumin in the development of drugs for CF pharmacotherapy: combined effects with genistein In: Curcumin: Biosynthesis, Medicinal Uses and Health Benefits (2012)
  • Author(s): Sohma Y, Yu YC, Miki H, Nakamura Y, Hanyuda A, Lin HY, Yasui M, Bompadre SGand Hwang TC
  • Total Pages: 223 - 234
  • Publisher: Editors Sasaki J & KichidaM, Nova Science Publishers, Hauppauge, New York, USA.
• [Book] Application of high-resolution single-channel recording to functional studies of cystic fibrosis mutants. In: Cystic Fibrosis Protocols and Diagnosis, Methods in Molecular Biology, 741 (2011)
  • Author(s): Cai Z, Sohma Y, Bompadre SG, Sheppard DN and Hwang TC、Editors Amaral MD & Kunzelmann K
  • Total Pages: 419- 441
  • Publisher: Humana Press, Totowa, New Jersey, USA
• [Remarks] (1) 慶應義塾大学医学部薬理学教室
  • URL: http://www.pharm.med.keio.ac.jp/about/sohma.html
• [Remarks] (2) John M. Dalton Cardiovascular ResearchCenter, Univ of Missouri - Columbia, MO, USA
  • URL: http://dalton.missouri.edu/investigators/sohmay.php