Membrane integration and intracellular localization of microsomal cytochrome P450

微粒体细胞色素 P450 的膜整合和细胞内定位

• 批准号: 09680598
• 负责人: SAKAGUCHI Masao
• 金额: $ 2.3万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680598/
• 关键词: endoplasmic reticulum; signal sequence; membrane topology; membrane protein; cytochrome P450; チトクロームP450; シナプトタグミン; 蛋白質分解

Using cytochrome P450 molecule as a typical model of endoplasmic reticulum membrane protein, we investigated its biosynthesis, integration into membrane, and localization in endoplasmic reticulum, and have demonstrated the follows :(1) Type I signal-anchor sequence (SA-I) which is essential for correct folding of P450 molecule shows a key role of topogenic sequence during membrane integration of multispanning membrane proteins.(2) For membrane integration of SA-I, a amino acid resides which induce turn structure are essential, when the amino-terminal domain is tend to form tight secondary structure.(3)The length of hydrophobic segment of SA-I is one of the key determinants of intracellular location of ER.(4) SA-I is integrated into the membrane just after the hydrophobic segment emerges from ribosomes.(5) NADPH-cytochrome P450 reductase also possesses SA-I as P450 molecule does.

以细胞色素P450分子作为典型的内质网膜蛋白模型，研究了其生物合成、整合入膜和在内质网中的定位，结果表明：（1）Ⅰ型信号锚定序列（SA-Ⅰ）是P450分子正确折叠所必需的，它在多跨膜蛋白的膜整合过程中起着关键的拓扑序列作用。(2)对于SA-Ⅰ的膜整合，当氨基端结构域倾向于形成紧密的二级结构时，诱导转角结构的氨基酸残基是必需的。（3）SA-Ⅰ疏水链段的长度是决定ER在细胞内定位的关键因素之一。(4)SA-I在疏水片段从核糖体中出现后立即整合到膜中。(5)NADPH-细胞色素P450还原酶也具有与P450分子相同的SA-Ⅰ。

项目成果

Nakamura, N., Yamazaki, S., Sato, K., Nakano, A., Sakaguchi, M.and Mihara, K.: ""Identification of potential regulatory elements for the transport of Emp24."" Mol.Biol.Cell. 9. 3493-3503 (1998)

Nakamura, N.、Yamazaki, S.、Sato, K.、Nakano, A.、Sakaguchi, M. 和 Mihara, K.：““鉴定 Emp24 运输的潜在调控元件。”Mol.Biol.Cell

阪口 雅郎: "マルチスパン膜タンパク質の立体構造形成:親水性膜貫通セグメントの組み込みをも説明する新しいモデル." 細胞工学. 18. 102-112 (1998)

Masao Sakaguchi：“多跨膜蛋白的结构形成：一种新模型，也解释了亲水性跨膜片段的合并。细胞工程”18。102-112（1998）

Heijne,G.von: "Membrane Protein Assembly" Chapman & Hall, 270 (1997)

Heijne,G.von：“膜蛋白组装”查普曼

Kida,Y.: "Membrane topology of NADPH-cytochrome P450 reductase on the endoplasmic reticulum." Arch.Biochem.Biophys.(in press). (1998)

Kida,Y.：“内质网上 NADPH-细胞色素 P450 还原酶的膜拓扑结构。”

Makishima, T., Nakashima, T., Nagata-Kuno, K., Fukushima, K., Iida, H., Sakaguchi, M., Ikehara, Y., Komiyama, S.and Nishimoto, T.: ""The highly conserved DAD1 protein involved in apoptosis is required for N-linked glycosylation."" Genes to Cells. 2. 129-1

槙岛，T.，中岛，T.，永田久野，K.，福岛，K.，饭田，H.，坂口，M.，池原，Y.，小宫山，S.和西本，T.：“”