Crystal structure analyses of cooperative oxygen-binding intermediates of giant hemoglobin

• Project/Area Number: 25870200
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Structural biochemistry; Biophysics
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: NUMOTO Nobutaka 東京医科歯科大学, 難治疾患研究所, 助教 (20378582)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ヘモグロビン / 協同性 / 構造変化 / X線結晶構造解析 / 中間体 / 構造生物 / 四次構造

Outline of Final Research Achievements

The crystals of the giant hemoglobin (V2Hb) from an invertebrate were transformed from the oxygenated to the deoxygenated state in keeping a crystalline structure. We have performed X-ray crystal structure analyses of various intermediate states between the oxy and deoxy forms of V2Hb. The electron densities of the oxygen molecules at the heme pockets (oxygen binding sites) gradually became very week or disappeared. The ternary structural changes occur primarily at AB-loop region of some subunits. The quaternary rearrangement of V2Hb might arise just before a complete dissociation of all the oxygen molecules from all the subunits.

Research Products

• [Journal Article] The structure of a deoxygenated 400 kDa hemoglobin reveals ternary and quaternary structural changes of giant hemoglobins (2014)
  • Author(s): Numoto, N., Nakagawa, T., Ohara, R., Hasegawa, T., Kita, A., Yoshida, T., Maruyama, T., Imai, K., Fukumori, Y., and Miki, K.
  • Journal Title: Acta Crystallogr D Biol Crystallogr. Volume: 70 Issue: 7 Pages: 1823-1831
  • DOI: 10.1107/s1399004714008475
  • Peer Reviewed
• [Presentation] ヘモグロビン分子の多様性 -巨大ヘモグロビンの構造と協同性機構- (2015)
  • Author(s): 沼本修孝
  • Organizer: 崎大学テニュアトラック推進機構医学系物質科学分野セミナー
  • Place of Presentation: 宮崎大学（宮崎）
  • Year and Date: 2015-03-23
  • Invited
• [Presentation] 巨大ヘモグロビン結晶中での酸素解離に伴う構造変化 (2014)
  • Author(s): 沼本修孝，中川太郎，喜田昭子，伊藤暢聡，福森義宏，三木邦夫
  • Organizer: 日本結晶学会2014年度年会
  • Place of Presentation: 東京大学（東京）
  • Year and Date: 2014-11-01 – 2014-11-03
• [Presentation] 巨大ヘモグロビン結晶内でのoxy型からdeoxy型への移行 (2014)
  • Author(s): 沼本修孝，中川太郎，喜田昭子，伊藤暢聡，福森義宏，三木邦夫
  • Organizer: 第52回日本生物物理学会年会
  • Place of Presentation: 札幌コンベンションセンター（北海道）
  • Year and Date: 2014-09-25
• [Presentation] Partial oxygen-dissociation of crystalline giant hemoglobin (2014)
  • Author(s): Numoto N., Nakagawa T., Kita A., Ito N., Fukumori Y., Miki K.
  • Organizer: XXIII Congress and General Assembly of the International Union of Crystallography
  • Place of Presentation: Palais des congrès de Montréal, Montreal (Canada)
  • Year and Date: 2014-08-06 – 2014-08-07
• [Presentation] 巨大ヘモグロビン結晶内における酸素解離過程 (2014)
  • Author(s): 沼本修孝，中川太郎，喜田昭子，伊藤暢聡，福森義宏，三木邦夫
  • Organizer: 第14回日本蛋白質科学会年会
  • Place of Presentation: ワークピア横浜（神奈川）
  • Year and Date: 2014-06-27
• [Presentation] 巨大ヘモグロビン結晶中での酸素結合状態の操作 (2013)
  • Author(s): 沼本修孝・中川太郎・喜田昭子・伊藤暢聡・福森義宏・三木邦夫
  • Organizer: 平成25年度日本結晶学会年会
  • Place of Presentation: 熊本大学（熊本県熊本市）