Structure and function of sensor proteins that regulate biological functions by gas molecules

• Project/Area Number: 23350084
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemistry related to living body
• Research Institution: Okazaki Research Facilities, National Institutes of Natural Sciences
• Principal Investigator: AONO Shigetoshi 大学共同利用機関法人自然科学研究機構(岡崎共通研究施設), 岡崎統合バイオサイエンスセンター, 教授 (60183729)
• Project Period (FY): 2011-11-18 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000); Fiscal Year 2013: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2012: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
• Keywords: センサータンパク質 / ヘムタンパク質 / 転写調節因子 / 走化性制御系 / シグナルトランスデューサー / 酸素センサー

Research Abstract

A chemotaxis signal transducer protein Aer2 from Pseudomonas aeruginosa was found to be a novel heme-based oxygen sensor protein. The crystal structure of Aer2 was determined, which reveals that a hydrogen bonding interaction between heme-bound oxygen and Trp283 in the distal heme pocket plays an important role for oxygen sensing and signal transduction of Aer2.
A novel heme sensor protein HrtR was also found in this work. The molecular mechanisms of heme sensing by HrtR and of the heme-responsive functional regulation of HrtR were elucidated by determining its crystal structure.

Research Products

• [Journal Article] A model theoretical study on ligand exchange reactions of CooA (2014)
  • Author(s): T. Ishida, S. Aono
  • Journal Title: Phys. Chem. Chem. Phys Volume: 15 Issue: 16 Pages: 6139-6148
  • DOI: 10.1039/c3cp43253j
  • Peer Reviewed
• [Journal Article] The Dos family of globin-related sensors using PAS domains to accommodate haem acting as the active site for sensing external signals (2013)
  • Author(s): S.Aono
  • Journal Title: Adv. Microbial Physiol Volume: 63 Pages: 273-327
  • DOI: 10.1016/b978-0-12-407693-8.00007-8
  • ISBN: 9780124076938
  • Peer Reviewed
• [Journal Article] Structural basis for the transcriptional regulation of heme homeostasis in Lactococcus lactis (2012)
  • Author(s): H. Sawai, M. Yamanaka, H. Sugimoto, Y. Shiro, S. Aono
  • Journal Title: J. Biol. Chem Volume: 287 Pages: 30755-30768
  • Peer Reviewed
• [Journal Article] Structural dynamics of proximal heme pocket in HemAT-Bs associated with O2 dissociation (2012)
  • Author(s): Y. Yoshida, H. Ishikawa, S. Aono, Y. Mizutani
  • Journal Title: Biochem. Biophys. Acta - Proteins and Proteomics Volume: 1824 Issue: 7 Pages: 866-872
  • DOI: 10.1016/j.bbapap.2012.04.007
  • Peer Reviewed
• [Journal Article] Site-specific protein dynamics in communication pathway from sensor to signaling domain of oxygen sensor protein, HemAT-Bs : time-resolved ultraviolet resonance Raman study (2012)
  • Author(s): S. El-Mashtoly, M. Kubo, Y. Gu, H. Sawai, S. Nakashima, T. Ogura, S. Aono, T. Kitagawa
  • Journal Title: J. Biol. Chem Volume: 287 Issue: 24 Pages: 19973-19984
  • DOI: 10.1074/jbc.m112.357855
  • Peer Reviewed
• [Journal Article] Structural Basis for Oxygen Sensing and Signal Transduction of the Heme-Based Sensor Protein Aer2 from Pseudomonas aeruginosa (2012)
  • Author(s): H. Sawai, H. Sugimoto, Y. Shiro, H. Ishikawa, Y. Mizutani, S. Aono
  • Journal Title: Chem. Commun Volume: 48 Issue: 52 Pages: 6523-6525
  • DOI: 10.1039/c2cc32549g
  • Peer Reviewed
• [Journal Article] Novel bacterial gas sensor proteins with transition-metal-containing prosthetic groups as active sites (2012)
  • Author(s): S. Aono
  • Journal Title: Antioxd. Redox Signal Volume: 16 Issue: 7 Pages: 678-686
  • DOI: 10.1089/ars.2011.4248
  • Peer Reviewed
• [Journal Article] Structural basis for the transcriptional regulation of heme homeostasis in Lactococcus lactis (2012)
  • Author(s): H. Sawai
  • Journal Title: J. Biol. Chem. Volume: 287 Issue: 36 Pages: 30755-30768
  • DOI: 10.1074/jbc.m112.370916
  • Peer Reviewed
• [Journal Article] Aldoxime dehydratase : probing the heme environment involved in the synthesis of the carbon-nitrogen triple bond (2011)
  • Author(s): E.Pinakoulaki, C.Koutsoupakis, H.Sawai, A.Pavlou, Y.Kato, Y.Asano, S.Aono
  • Journal Title: J.Phys.Chem.B Volume: 115 Issue: 44 Pages: 13012-13018
  • DOI: 10.1021/jp205944e
  • Peer Reviewed
• [Presentation] Structural basis for the molecular mechanism of dehydration reaction catalyzed by a novel heme protein (2014)
  • Author(s): S. Aono
  • Organizer: 225th The Electrochemical Society Meeting
  • Place of Presentation: Orlando, USA
  • Invited
• [Presentation] Molecular mechanisms of signal transduction upon oxygen sensing by the heme-based sensor protein Aer2 (2014)
  • Author(s): S. Aono
  • Organizer: 8th International Conference on Porphyrins and Phthalocyanines
  • Place of Presentation: Istanul, Turkey
  • Invited
• [Presentation] Structural basis for the transcriptional regulation of heme homeostasis in Lactococuus lactis (2013)
  • Author(s): S. Aono
  • Organizer: 6th Japan-Korea Seminar on Biomolecular Sciences Experiments and Simulations
  • Place of Presentation: Okazaki, Japan
• [Presentation] Biological signal transduction using heme as a signaling molecule (2013)
  • Author(s): 青野重利
  • Organizer: 錯体化学会第63回討論会
  • Place of Presentation: 琉球大学・沖縄
• [Presentation] ヘム含有センサータンパク質Aer2による選択的酸素センシングの分子機構 (2013)
  • Author(s): 澤井仁美, 杉本宏, 城宜嗣, 青野重利
  • Organizer: 第112回触媒討論会
  • Place of Presentation: 秋田大学・秋田
• [Presentation] Molecular mechanisms of the transcriptional regulation by heme sensing (2013)
  • Author(s): H. Sawai, H. Sugimoto, Y. Shiro, S. Aono
  • Organizer: 16th International Biological Inorganic Chemistry
  • Place of Presentation: Grenoble, France
• [Presentation] Protein conformational dynamics and kinetic properties of the oxygen-sensing signal transducer protein HemAT as revealed by time-resolved step-scan FTIR spectroscopy (2013)
  • Author(s): A. Pavlou, E. Pinakoulaki, H. Yoshimura, S. Aono
  • Organizer: 16th International Biological Inorganic Chemistry
  • Place of Presentation: Grenoble, France
• [Presentation] Structural changes in the heme and heme pocket upon CO dissociation of CooA observed by time-resolved resonance Raman spectroscopy (2013)
  • Author(s): A. Otomo, H. Ishikawa, M. Mizuno, Y. Mizutani, S. Aono
  • Organizer: 16th International Biological Inorganic Chemistry
  • Place of Presentation: Grenoble, France
• [Presentation] Structural basis for the transcriptional regulation of heme homeostasis (2013)
  • Author(s): S. Aono, H. Sawai, M. Yamanaka, H. Sugimoto, Y. Shiro
  • Organizer: 4th International Symposium on Metallomics
  • Place of Presentation: Oviedo, Spain
• [Presentation] 走化性シグナルトランスデューサータンパク質Aer2の構造と機能 (2013)
  • Author(s): 澤井仁美, 杉本宏, 城宜嗣, 青野重利
  • Organizer: 第40回生体分子科学討論会
  • Place of Presentation: 大阪大学・大阪
• [Presentation] Signal sensing and signal transduction in heme sensor proteins (2013)
  • Author(s): S. Aono
  • Organizer: 223rd The Electrochemical Society Meeting
  • Place of Presentation: Toronto, Canada
• [Presentation] Transcriptional regulation of heme homeostasis in Lactococcus lactis (2013)
  • Author(s): S. Aono, H. Sawai, M. Yamanaka, H. Sugimoto, Y. Shiro
  • Organizer: International Bio-iron Meeting 2013
  • Place of Presentation: London, UK
• [Presentation] 時間分解共鳴ラマン分光法を用いた酸素センサータンパク質HemATの酸素脱離に伴う構造変化観測 (2013)
  • Author(s): 石川春人, 吉田祐, 青野重利, 水谷泰久
  • Organizer: 日本化学会第93春季年会
  • Place of Presentation: 立命館大学・滋賀
• [Presentation] Structural Basis for Oxygen Sensing and Signal Transduction of the Heme-based Sensor Protein Aer2 (2013)
  • Author(s): H. Sawai, H. Sugimoto, Y. Shiro, S. Aono
  • Organizer: 5th Korea-Japan Seminar on Biomolecular Sciences Experiments and Simulations
  • Place of Presentation: Seoul, Korea
• [Presentation] Signal sensing and signal transduction in heme sensor proteins (2013)
  • Author(s): S. Aono
  • Organizer: 223rd The Electrochemical Society Meeting
  • Place of Presentation: Tronto, Canada
  • Invited
• [Presentation] Identification of active-site residues in heme detoxification protein (2013)
  • Author(s): H. Ishikawa
  • Organizer: 16th International Biological Inorganic Chemistry
  • Place of Presentation: Grenoble, France
• [Presentation] Structural basis for the transcriptional regulation of heme homeostasis in Lactococuus lactis (2013)
  • Author(s): S. Aono
  • Organizer: 6th Japan-Korea Seminar on Biomolecular Sciences Experiments and Simulations
  • Place of Presentation: 岡崎コンファレンスセンター（愛知県岡崎市）, Japan
  • Invited
• [Presentation] 走化性シグナルトランスデューサータンパク質Aer2の構造と機能 (2013)
  • Author(s): 青野重利
  • Organizer: 第４０回生体分子科学討論会
  • Place of Presentation: 大阪大学（大阪府吹田市）
• [Presentation] ヘム含有センサータンパク質Aer2による選択的酸素センシングの分子機構 (2013)
  • Author(s): 青野重利
  • Organizer: 第１１２回触媒討論会
  • Place of Presentation: 秋田大学（秋田県秋田市）
• [Presentation] Biological signal transduction using heme as a signaling molecule (2013)
  • Author(s): 青野重利
  • Organizer: 錯体化学会第６３回討論会
  • Place of Presentation: 琉球大学（沖縄県那覇市）
• [Presentation] Listeria monocytogenes のヘム取込み系におけるヘム結合タンパク質HupDの性質 (2013)
  • Author(s): 岡本泰典
  • Organizer: 日本化学会第９３春季年会
  • Place of Presentation: 立命館大学、滋賀
• [Presentation] 時間分解共鳴ラマン分光法を用いた酸素センサータンパク質HemATの酸素脱離に伴う構造変化観測 (2013)
  • Author(s): 石川春人
  • Organizer: 日本化学会第９３春季年会
  • Place of Presentation: 立命館大学、滋賀
• [Presentation] Molecular mechanism of heme-responsive transcriptional regulation (2012)
  • Author(s): S. Aono
  • Organizer: 6th Asian Biological Inorganic Chemistry Conference
  • Place of Presentation: Hong Kong, China
• [Presentation] 細胞内ヘム濃度の恒常性維持に関わる転写制御の分子機構 (2012)
  • Author(s): 澤井仁美, 杉本宏, 山中優, 城宜嗣, 青野重利
  • Organizer: 日本結晶学会年会
  • Place of Presentation: 東北大学・宮城
• [Presentation] ヘムをエフェクター分子とする転写調節因子HrtRの構造と機能 (2012)
  • Author(s): 澤井仁美, 杉本宏, 山中優, 城宜嗣, 青野重利
  • Organizer: 錯体化学会第62回討論会
  • Place of Presentation: 富山大学・富山
• [Presentation] Crystal structures of heme-sensing transcriptional regulator responsible for heme homeostasis in Lactococcus lactis (2012)
  • Author(s): H. Sawai, M. Namanaka, H. Sugimoto, Y. Shiro, S. Aono
  • Organizer: 11th European Biological Inorganic Chemistry Conference
  • Place of Presentation: Granada, Spain
• [Presentation] ヘム濃度の恒常性維持に関わる転写調節因子HrtRの分子機構 (2012)
  • Author(s): 澤井仁美, 杉本宏, 山中優, 城宜嗣, 青野重利
  • Organizer: 第6回バイオ関連化学シンポジウム
  • Place of Presentation: 北海道大学・北海道
• [Presentation] Structural basis for the transcriptional regulation of heme homeostasis in lactic acid bacteria (2012)
  • Author(s): S. Aono, H. Sawai, M. Namanaka, H. Sugimoto, Y. Shiro
  • Organizer: 8th International Biometals Symposium
  • Place of Presentation: Brussels, Belgium
• [Presentation] Structural basis for the transcriptional regulation of heme homeostasis in lactic acid bacterium, Lactococcus lactis (2012)
  • Author(s): S. Aono
  • Organizer: 7th International Conference on Porphyrins and Phthalocyanines
  • Place of Presentation: Jeju, Korea
• [Presentation] ヘム濃度の恒常性維持に関わる転写調節因子の構造と機能 (2012)
  • Author(s): 澤井仁美, 杉本宏, 山中優, 城宜嗣, 青野重利
  • Organizer: 第12回日本蛋白質科学会年会
  • Place of Presentation: 名古屋国際会議場・愛知
• [Presentation] ヘム分子により機能制御される転写調節因子HrtRの構造と機能 (2012)
  • Author(s): 澤井仁美, 杉本宏, 山中優, 城宜嗣, 青野重利
  • Organizer: 第39回生体分子科学討論会
  • Place of Presentation: 東北大学・宮城
• [Presentation] Transcriptional regulation by heme acting as a signaling molecule (2012)
  • Author(s): S. Aono
  • Organizer: 221st The Electrochemical Society Meeting
  • Place of Presentation: Seattle, USA
• [Presentation] ヘムをセンシングする転写調節因子HrtRの機能制御機構 (2012)
  • Author(s): 山中優, 澤井仁美, 青野重利
  • Organizer: 日本化学会第92春季年会
  • Place of Presentation: 慶応義塾大学・神奈川
• [Presentation] 新規な転写調節因子HrtRのヘムによる機能制御の分子機構 (2012)
  • Author(s): 澤井仁美, 杉本宏, 山中優, 城宜嗣, 青野重利
  • Organizer: 日本化学会第92春季年会
  • Place of Presentation: 慶応義塾大学・神奈川
• [Presentation] Structural basis for the transcriptional regulation of heme homeostasis in Lactococcus lactis (2012)
  • Author(s): H. Sawai, M. Namanaka, H. Sugimoto, Y. Shiro, S. Aono
  • Organizer: 4th Japan-Korea Seminar on Biomolecular Sciences Experiments and Simulations
  • Place of Presentation: Nara, Japan
• [Presentation] X-ray crystal structure of Michaelis complex of aldoxime dehydratase, a new heme-containing hydrolyase (2012)
  • Author(s): S. Aono
  • Organizer: EMBO Conference: Catalytic Mechanisms by Biological Systems
  • Place of Presentation: Groningen, Netherlands
• [Presentation] Structural basis for the transcriptional regulation of heme homeostasis in Lactococcus lactis (2012)
  • Author(s): H. Sawai
  • Organizer: The 1st International Symposium on Biofunctional Chemistry
  • Place of Presentation: Tokyo, Japan
• [Presentation] ヘム濃度の恒常性維持に関わる転写調節因子の構造と機能 (2012)
  • Author(s): 澤井仁美
  • Organizer: 第１２回日本蛋白質科学会年会
  • Place of Presentation: 名古屋国際会議場、名古屋
• [Presentation] ヘム分子により機能制御される転写調節因子HrtRの構造と機能 (2012)
  • Author(s): 青野重利
  • Organizer: 第３９回生体分子科学討論会
  • Place of Presentation: 東北大学、仙台
• [Presentation] ヘム濃度の恒常性維持に関わる転写調節因子HrtRの分子機構 (2012)
  • Author(s): 澤井仁美
  • Organizer: 第６回バイオ関連化学シンポジウム
  • Place of Presentation: 北海道大学、北海道
• [Presentation] ヘムをエフェクター分子とする転写調節因子HrtRの構造と機能 (2012)
  • Author(s): 青野重利
  • Organizer: 錯体化学会 第６２回討論会
  • Place of Presentation: 富山大学、富山
• [Presentation] 細胞内ヘム濃度の恒常性維持に関わる転写制御の分子機構 (2012)
  • Author(s): 澤井仁美
  • Organizer: 日本結晶学会年会
  • Place of Presentation: 東北大学、仙台
• [Presentation] ヘム分子により機能制御される転写調節因子HrtRの構造と機能 (2012)
  • Author(s): 青野重利
  • Organizer: 第３９回生体分子科学討論会
  • Place of Presentation: 東北大学（宮城県）
• [Presentation] ヘム濃度の恒常性維持に関わる転写調節因子の構造と機能 (2012)
  • Author(s): 澤井仁美
  • Organizer: 第１２回日本蛋白質科学会年会
  • Place of Presentation: 名古屋国際会議場（愛知県）
• [Presentation] ヘム濃度の恒常性維持に関わる転写調節因子HrtRの分子機構 (2012)
  • Author(s): 澤井仁美
  • Organizer: 第６回バイオ関連化学シンポジウム
  • Place of Presentation: 北海道大学（北海道）
• [Presentation] ヘムをエフェクター分子とする転写調節因子HrtRの構造と機能 (2012)
  • Author(s): 青野重利
  • Organizer: 錯体化学会 第６２回討論会
  • Place of Presentation: 富山大学（富山県）
• [Presentation] Crystal structures of heme-sensing transcriptional regulator responsible for heme homeostasis in Lactococcus lactis (2012)
  • Author(s): S. Aono
  • Organizer: 11th European Biological Inorganic Chemstry Conference
  • Place of Presentation: Granada, Spain
• [Presentation] Structural basis for the transcriptional regulation of heme homeostasis in lactic acid bacteria (2011)
  • Author(s): H. Sawai, M. Namanaka, H. Sugimoto, Y. Shiro, S. Aono
  • Organizer: 11th International Symposium on Applied Biological Inorganic Chemistry
  • Place of Presentation: Barcelona, Spain
• [Presentation] ヘムが関与するシグナルセンシング・シグナル伝達の分子機構 (2011)
  • Author(s): 青野重利
  • Organizer: 日本生化学会九州支部例会
  • Place of Presentation: 久留米大学（福岡県）
  • Invited
• [Presentation] ヘムをセンシングする転写調節因子YgfCの構造と機能 (2011)
  • Author(s): 山中優
  • Organizer: 第１１回日本蛋白質科学会年会
  • Place of Presentation: ホテル阪急（大阪府）
• [Presentation] ヘムをシグナル分子とする遺伝子発現制御の分子機構 (2011)
  • Author(s): 青野重利
  • Organizer: 第３８回生体分子科学討論会
  • Place of Presentation: 筑波大学（茨城県）
• [Presentation] Biological Sensing and Signal Transduction Systems with a Heme (2011)
  • Author(s): S. Aono
  • Organizer: 15th International Conference on Biological Inorganic Chemistry
  • Place of Presentation: Vancouver, Canada
  • Invited
• [Presentation] Structural characterization of Aer2 that adopts a heme-containing PAS domain as a sensor for aerotaxis control (2011)
  • Author(s): H. Sawai
  • Organizer: 15th International Conference on Biological Inorganic Chemistry
  • Place of Presentation: Vancouver, Canada
• [Presentation] Ultraviolet time-resolved resonance Raman investigation of structural dynamics of HemAT-Bs following CO photodissociation (2011)
  • Author(s): T. Kitagawa
  • Organizer: 15th International Conference on Biological Inorganic Chemistry
  • Place of Presentation: Vancouver, Canada
• [Presentation] ヘムセンサー機能を有する転写調節因子の構造と機能 (2011)
  • Author(s): 青野重利
  • Organizer: 第６１回錯体化学討論会
  • Place of Presentation: 岡山理科大学（岡山県）
• [Presentation] ヘムをシグナル分子とする生体機能制御の分子機構 (2011)
  • Author(s): 青野重利
  • Organizer: 第１０８回触媒討論会
  • Place of Presentation: 北見工業大学（北海道）
  • Invited
• [Presentation] ヘムにより機能制御される新規な転写調節因子HesRのX線結晶構造 (2011)
  • Author(s): 澤井仁美
  • Organizer: 日本結晶学会年会
  • Place of Presentation: 北海道大学（北海道）