Organelle selective targeting of ABC subfamily D proteins and molecular mechanisms of their functions on the membranes

• Project/Area Number: 20590054
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: University of Toyama
• Principal Investigator: IMANAKA Tsuneo University of Toyama, 大学院・医学薬学研究部(薬学), 教授 (50119559)
• Co-Investigator(Kenkyū-buntansha): KASHIWAYAMA Yoshinori 富山大学, 大学院・医学薬学研究部(薬学), 助教 (20401812)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ABCタンパク質 / ペルオキシソーム / 小胞体 / 局在化機構 / 基質輸送機構 / 脂肪酸輸送 / Pex19p / Pex3p / X線結晶構造解析 / Pex19P / 基質輪送機 / 結晶化 / ATP結合・加水分解

Research Abstract

We found that the hydrophobic properties of NH_2-terminal cytosolic region of ABC subfamily D proteins determine their subcellular localization. ABC proteins (ABCD1～3) with the NH_2-terminal hydrophobic region are targeted to peroxisomes through the interaction of ABCD1～3 to Pex19p and Pex3p. On the other hand, ABCD4 without the hydrophobic region is targeted to endoplasmic reticulum. Concerning function of ABC subfamily D proteins, ABCD1～3 are suggested to be involved in transport to acyl-CoA and ABCD4 is involved in heme metabolism.

Research Products

• [Journal Article] The structure of Physarum polycephalun hemaggulutinin I suggests a minimal carbohydrate recognition domain of legume lectin fold. (2011)
  • Author(s): Kouno T., et al.
  • Journal Title: J. Mol. Biol. Volume: 405 Pages: 560-569
  • Peer Reviewed
• [Journal Article] Structural basis for docking of peroxisomal membrane protein carrier Pex19p onto its receptor Pex3p. (2010)
  • Author(s): Sato Y., Shibata H., Nakatsu T., Nakano H., Kashiwayama Y., Imanaka T., Kato H.
  • Journal Title: EMBO J. 29 Pages: 4083-4093
  • Peer Reviewed
• [Journal Article] Identification of a substrate-binding site in a peroxisomal β-oxidation enzyme by photoaffinity labeling with a novel palmitoyl derivative. (2010)
  • Author(s): Kashiwayama Y., Tomohiro T., Narita K., Suzumura M., Glumoff T., Hiltunen J.K., Van Veldhoven P.P., Hatanaka Y., Imanaka T.
  • Journal Title: J.Biol.Chem. 285 Pages: 26315-26325
  • Peer Reviewed
• [Journal Article] Multiple organelle-targeting signals in the N-terminal portion of peroxisomal membrane protein PMP70. (2010)
  • Author(s): Iwashita S., Tsuchida M., Tsukuda M., Yamashita Y., Emi Y., Kida Y., Komori M., Kashiwayama Y., Imanaka T., Sakaguchi M.
  • Journal Title: J.Biochem. 147 Pages: 581-590
  • NAID: 10027875314
  • Peer Reviewed
• [Journal Article] Structural basis for docking of peroxisomal membrane protein carrier Pexl9p onto its receptor Pex3p. (2010)
  • Author(s): Sato Y., et al.
  • Journal Title: EMBO J. Volume: 29 Pages: 4083-4093
  • Peer Reviewed
• [Journal Article] Identification of a substrate-binding site in a peroxisomal n-oxidation enzyme by photoaffinity labeling with a novel palmitovl derivative. (2010)
  • Author(s): Kashiwayama Y., et al.
  • Journal Title: J. Biol. Chem. Volume: 285 Pages: 26315-26325
  • Peer Reviewed
• [Journal Article] Lipid rafts are essential for peroxisome biogenesis in HepG2 cells. (2010)
  • Author(s): Woudenberg J., et al.
  • Journal Title: Hepatology Volume: 52 Pages: 623-633
  • Peer Reviewed
• [Journal Article] Multiple organelle-targeting signals in the N-terminal portion of peroxisomal membrane protein PMP70. (2010)
  • Author(s): Iwashita, S.
  • Journal Title: J.Biochem. 147 Pages: 581-590
  • Peer Reviewed
• [Journal Article] 70-kDa peroxisomal membrane protein related protein(P70R/ABCD4)localizes to endoplasmic reticulum not peroxisomes, and NH_2-terminal hydrophobic property determines the subcellular localization of ABC subfamily D proteins. (2009)
  • Author(s): Kashiwayama Y., Seki M., Yasui A., Murasaki Y., Morita M., Sakaguchi M., Tanaka Y., Imanaka T.
  • Journal Title: Exp.Cell Res. 315 Pages: 190-205
  • Peer Reviewed
• [Journal Article] Tissue-specific expression and subcellular localization of ALADIN, the absence of which causes human triple A syndrome. (2009)
  • Author(s): Cho, A.R.
  • Journal Title: Exp.Mol.Med. 41 Pages: 381-386
  • Peer Reviewed
• [Journal Article] A novel immunoregulatory protein in human colostrum, syntenin-1, for promoting the development of IgA producing cells from cord blood B cells. (2009)
  • Author(s): Sira, M.M.
  • Journal Title: Int.Immunol. 21 Pages: 1013-1023
  • Peer Reviewed
• [Journal Article] Characterization of the interaction between recombinant human peroxin Pex3p and Pex19p : Identification of TRP104 in Pex3p as a critical residue for the interaction. (2008)
  • Author(s): Sato Y., Shibata H., Nakano H., Matsuzono Y., Kashiwayama Y., Kobayashi Y., Fujiki Y., Imanaka T., Kato H.
  • Journal Title: J.Biol.Chem. 283 Pages: 61346-61446
  • Peer Reviewed
• [Journal Article] Baicalein 5, 6, 7-trimethyl ether activates peroxisomal but not mitochondrial fatty acid β-oxidation (2008)
  • Author(s): Morita, M.
  • Journal Title: J. Inherit. Metab. Dis 31 Pages: 442-449
  • Peer Reviewed
• [Journal Article] Characterization of the interaction between recombinant human peroxin Pex3p and Pexl9p : Identification of TRP-104 in Pex3p as a critical residue for the interaction. (2008)
  • Author(s): Sato, Y.
  • Journal Title: J. Biol. Chem. 283 Pages: 6136-6144
  • Peer Reviewed
• [Journal Article] 70-kDa peroxisomal membrane protein related protein (p70R/ABCD4) localizes to endoplasmic reticulum not peroxisomes, and NH_2-terminal hydrophobic property determines the subcellular localization of ABC subfamily D proteins. (2008)
  • Author(s): Kashiwayama, Y.
  • Journal Title: Exp. Cell Res 315 Pages: 190-205
  • Peer Reviewed
• [Journal Article] 極長鎖脂肪酸代謝と疾患 (2008)
  • Author(s): 守田 雅志
  • Journal Title: 生化学 80 Pages: 434-439
  • Peer Reviewed
• [Presentation] ペルオキシソーム病の繊維芽細胞にみられる極長鎖脂肪酸含有脂質の分子構造決定 (2010)
  • Author(s): 西澤千穂, 他
  • Organizer: 第83回日本生化学会大会・第33回日本分子生物学会年会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] ペルオキシソーム形成因子Pex3pの存在状態とPex19pとの相互作用に伴う高次構造変化 (2010)
  • Author(s): 中野雄太, 他
  • Organizer: 第83回日本生化学会大会・第33回日本分子生物学会年会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] ペルオキシソーム膜raft様構造体の機能解析 (2010)
  • Author(s): 土屋裕貴, 他
  • Organizer: 第83回日本生化学会大会・第33回日本分子生物学会年会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] ペルオキシソーム膜形成因子Pex16pのペルオキシソーム局在化シグナルの解析 (2010)
  • Author(s): 五十嵐喜子, 他
  • Organizer: 第32回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 富山
  • Year and Date: 2010-11-30
• [Presentation] ABCタンパク質サブファミリーD群のオルガネラ選択的局在化機構 (2010)
  • Author(s): 柏山恭範, 他
  • Organizer: 第32回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 富山
  • Year and Date: 2010-11-29
• [Presentation] ER膜上に存在するABCタンパク質P70R(ABCD4)の機能解析 (2010)
  • Author(s): 東野和直, 他
  • Organizer: 日本薬学会北陸支部第122回例会
  • Place of Presentation: 金沢
  • Year and Date: 2010-11-21
• [Presentation] ABCタンパク質D群の細胞内局在化機構:ヒトと線虫間での共通性 (2010)
  • Author(s): 朝日彰子
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-29
• [Presentation] Organelle selective targeting of ABC subfamily D proteins : Importance of NH_2-terminal hydrophobic motifs. (2010)
  • Author(s): Imanaka, T.
  • Organizer: 3th FEBS Special Meeting
  • Place of Presentation: Innsbruck, Austria
  • Year and Date: 2010-03-02
• [Presentation] ABCタンパク質サブファミリーDの細胞内局在化とN末端アミノ酸配列 (2010)
  • Author(s): 李朝香, 朝日彰子, 赤池宗輔, 柏山恭範, 守田雅志, 安川洋生, 今中常雄
  • Organizer: 第83回日本生化学会大会・第33回日本分子生物学会年会合同大会
  • Place of Presentation: 神戸
• [Presentation] 小胞体膜上に存在するABCタンパク質P70R(ABCD4)の存在状態と機能の解析 (2010)
  • Author(s): 東野和直, 上杉泰介, 柏山恭範, 今中常雄
  • Organizer: 第83回日本生化学会大会・第33回日本分子生物学会年会合同大会
  • Place of Presentation: 神戸
• [Presentation] Organelle selective targeting of ABC subfamily D proteins : Importance of NH_2-terminal hydrophobic motifs. (2010)
  • Author(s): 今中常雄
  • Organizer: 3th FEBS Special Meeting : ATP-Binding Cassette(ABC)Proteins : From Multidrug Resistance to Genetic Diseases.
  • Place of Presentation: Innsbruck, Austria.
• [Presentation] ペルオキシソーム膜形成因子Pex16pのペルオキシソーム局在化メカニズムの解析 (2009)
  • Author(s): 五十嵐嘉子
  • Organizer: 日本薬学会北陸支部第121回例会
  • Place of Presentation: 富山
  • Year and Date: 2009-12-06
• [Presentation] Importance of the NH_2-terminal hydrophobic motifs on the peroxisome selective targeting of PMP70. (2009)
  • Author(s): 柏山恭範, 守田雅志, 今中常雄
  • Organizer: International Meeting on Peroxisome Research
  • Place of Presentation: Seattle, USA.
  • Year and Date: 2009-11-19
• [Presentation] Importance of the NH_2-terminal hydrophobic motifs on the peroxisome selective targeting of PMP70. (2009)
  • Author(s): Imanaka, T.
  • Organizer: International Meeting on Peroxisome Research
  • Place of Presentation: Seattle, USA
  • Year and Date: 2009-11-19
• [Presentation] Structural-basis for the Pex3p-Pex19p interaction in the translocation of class I peroxisomal membrane proteins. (2009)
  • Author(s): Shibata, H.
  • Organizer: International Meeting on Peroxisome Research
  • Place of Presentation: Seattle, USA
  • Year and Date: 2009-11-19
• [Presentation] ヒト由来ペルオキシソーム膜タンパク質輸送因子Pex3pとPex19pの構造基盤 (2009)
  • Author(s): 佐藤康彦
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-22
• [Presentation] Identification of a substrate-binding site in a peroxisomal β-oxidation enzyme by photoaffinity labeling with palmitoyl derivative. (2009)
  • Author(s): Kashiwayama, Y.
  • Organizer: The 5th Takeda Science Foundation Symposium on PharmaSciences
  • Place of Presentation: 東京
  • Year and Date: 2009-05-25
• [Presentation] ペルオキシソーム膜タンパク質局在化の分子機構 : PMP70をモデルタンパク質としての解析 (2009)
  • Author(s): 柏山恭範
  • Organizer: 日本生化学会北陸支部第27回大会
  • Place of Presentation: 福井
  • Year and Date: 2009-05-23
• [Presentation] ペルオキシソーム膜ABCタンパク質ABCD1欠損マウスにおける極長鎖脂肪酸蓄積の分子機構 (2009)
  • Author(s): 小松 史明
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2009-03-26
• [Presentation] ペルオキシソーム膜ABCタンパク質ABCD1機能欠損における極長鎖脂肪酸蓄積の分子機構 (2008)
  • Author(s): 小松 史明
  • Organizer: 第31回目本分子生物学会・第81回日本生化学会合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-09
• [Presentation] U87グリオブラストーマ細胞におけるペルオキシソーム膜ABCタンパク質ABCD1機能欠損によるコレステロール代謝異常 (2008)
  • Author(s): 守田 雅志
  • Organizer: 第31回日本分子生物学会・第81回日本生化学会合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-09
• [Presentation] ペルオキシソーム膜ABCタンパク質ABCDI欠損における極長鎖脂肪酸代謝 (2008)
  • Author(s): 小松 史明
  • Organizer: 日本薬学会北陸支部第118回例会
  • Place of Presentation: 北陸大学(金沢)
  • Year and Date: 2008-11-09
• [Presentation] ABCタンパク質D群の細胞内局在はN末端アミノ酸配列に依存する (2008)
  • Author(s): 柏山恭範, 関みどり, 安井暁奈, 守田雅志, 今中常雄
  • Organizer: 第30回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 札幌
  • Year and Date: 2008-08-07
• [Presentation] ABCタンパク質D群の細胞内局在はN末端アミノ酸配列に依存する (2008)
  • Author(s): 柏山 恭範
  • Organizer: 第30回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2008-08-07
• [Presentation] ペルオキシソーム膜タンパク質輸送に関与するPex3pとPex19pの相互作用様式 (2008)
  • Author(s): 佐藤 康彦
  • Organizer: 第8回蛋白質科学会年会
  • Place of Presentation: タワーホール船堀(東京)
  • Year and Date: 2008-06-12
• [Presentation] P70R (ABCD4)の細胞内局在と局在化機構の解析から明らかになるABCサブフアミリーD群タンパク質の細胞内局在制御機構 (2008)
  • Author(s): 柏山 恭範
  • Organizer: 第3回トランスポーター研究会年会
  • Place of Presentation: 京都大学
  • Year and Date: 2008-06-07
• [Presentation] ABCD群タンパク質の細胞内局在はN末端アミノ酸配列が制御している (2008)
  • Author(s): 柏山 恭範
  • Organizer: 日本生化学会北陸支部第26回大会
  • Place of Presentation: 金沢大学
  • Year and Date: 2008-05-31
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