Functional analysis of human ABC transporters involved in HDL generation.

参与 HDL 生成的人类 ABC 转运蛋白的功能分析。

• 批准号: 24780101
• 负责人: KIMURA Yasuhisa
• 金额: $ 3万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24780101/
• 关键词: ABCタンパク質; ABCG1; コレステロール; HDL; 膜輸送体; タンパク質精製; 高密度リポタンパク質; 能動輸送; 基質特異性; ABCG4; 脂質恒常性; 高脂血症

Cholesterol is an essential component for our body as a constituent of plasma membrane and precursor of steroid hormones. Since the excess cholesterol is harmful to cells, cholesterol homeostasis in peripheral tissues are tightly regulated. In this research, we purified human ABCG1 and ABCG4, and analyzed its substrate specificity by measuring ATPase activity.Purified ABCG1 showed the ATPase activity that comparable to those of active transporters. The ATPase activity of ABCG1, reconstituted in phosphatidylserine liposome, was stimulated by cholesterol and choline phospholipids (especially sphingomyelin). The ATPase activity of ABCG4 was stimulated in cholesterol containing liposomes. Unlike ABCG1, choline phospholipids showed no effects on the ATPase activity. Our results suggest that ABCG1 and ABCG4 are active lipid transporters and ABCG1 recognizes cholesterol and sphingomyelin as transport substrates, while ABCG4 is a cholesterol specific transporter.

胆固醇是我们身体的重要组成部分，是质膜的组成部分和类固醇激素的前体。由于过量的胆固醇对细胞有害，外周组织中的胆固醇稳态受到严格调节。本研究对人ABCG 1和ABCG 4进行了纯化，并通过ATP酶活性测定分析了其底物特异性，纯化的ABCG 1的ATP酶活性与活性转运蛋白的ATP酶活性相当。胆固醇和胆碱磷脂（尤其是鞘磷脂）可刺激ABCG 1在磷脂酰丝氨酸脂质体中重构的ATP酶活性。ABCG 4的ATP酶活性在含胆固醇的脂质体中被刺激。与ABCG 1不同，胆碱磷脂对ATP酶活性没有影响。我们的研究结果表明，ABCG 1和ABCG 4是积极的脂质转运和ABCG 1识别胆固醇和鞘磷脂作为运输底物，而ABCG 4是胆固醇特异性转运。

项目成果

精製タンパク質を用いたヒトABCB6の機能解析

使用纯化蛋白对人 ABCB6 进行功能分析

• 发表时间: 2013
• 作者: Xue Bai;Mayo Sakaguchi;Yuko Yamaguchi;Shiori Ishihara;Masuhiro Tsukada;Kimio Hirabayashi;Kousaku Ohkawa;Takaomi Nomura;Ryoichi Arai;大貫元
• 通讯作者: 大貫元

Analysis of the substrate specificity of ABCB6

ABCB6的底物特异性分析

• 发表时间: 2013
• 作者: Yoshinaga S;Sato T;Hirakane M;Esaki K;Hamaguchi T;Haga-Yamanaka S;Tsunoda M;Kimoto H;Shimada I;Touhara K;Terasawa H;Hajime Ohnuki
• 通讯作者: Hajime Ohnuki

Characterization of the substrate specificity of ABCB6

ABCB6 底物特异性的表征

• 发表时间: 2013
• 作者: Takako Shiono;Takaomi Nomura1;Yoshiaki Nishiya;Ryoichi Arai;Hajime Ohnuki
• 通讯作者: Hajime Ohnuki

脂質輸送型ABCタンパク質の基質認識

脂质转运 ABC 蛋白的底物识别

• 发表时间: 2014
• 期刊: 輸送機構
• 作者: M. Oku;Y Maeda;and Y. Sakai;木村泰久
• 通讯作者: 木村泰久

Substrate recognition of human ABCG1 and ABCG4

人类 ABCG1 和 ABCG4 的底物识别

• 发表时间: 2014
• 作者: Yasuhisa Kimura;Hiroshi Hirayama;Noriyuki Kioka;Michinori Matsuo;Kazumitsu Ueda
• 通讯作者: Kazumitsu Ueda