UCP3 is associated with Hax-1 in mitochondria in the presence of calcium ion.

UCP3 is associated with Hax-1 in mitochondria in the presence of calcium ion.
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DOI:
10.1016/j.bbrc.2016.02.075
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发表时间:
2016-03-25
影响因子:
3.1
通讯作者:
Nikawa, Takeshi
Nikawa, Takeshi
中科院分区:
生物学4区
文献类型:
--
作者:
Hirasaka, Katsuya;Mills, Edward M.;Haruna, Marie;Bando, Aki;Ikeda, Chika;Abe, Tomoki;Kohno, Shohei;Nowinski, Sara M.;Lago, Cory U.;Akagi, Ken-ichi;Tochio, Hidehito;Ohno, Ayako;Teshima-Kondo, Shigetada;Okumura, Yuushi;Nikawa, Takeshi

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解偶联蛋白3(UCP 3)是已知的调节能量耗散,质子泄漏,脂肪酸氧化和氧化应激。为了鉴定UCP 3的推定蛋白调节剂,我们进行了酵母双杂交筛选。在这里,我们报告,UCP 3与HS-1相关蛋白X-1(Hax-1),一种抗凋亡蛋白,定位于线粒体,并参与细胞对Ca 2+的反应。环2内的亲水序列,和小鼠UCP 3的基质定位的亲水结构域,是必要的结合到Hax-1的C-末端结构域,邻近线粒体内膜。有趣的是,这些蛋白质的相互作用发生在钙依赖性的方式。此外,Hax-1的C-末端结构域的NMR谱显着改变的Ca 2+的去除,表明Hax-1的C-末端结构域进行了Ca 2+诱导的构象变化。在无Ca ~(2+)状态下,Hax-1的C端倾向于展开,表明Ca ~(2+)结合可能诱导Hax-1 C端的蛋白质折叠。这些结果表明UCP 3-Hax-1复合物可能调节线粒体Ca 2+引起的线粒体功能变化。
Uncoupling protein 3 (UCP3) is known to regulate energy dissipation, proton leakage, fatty acid oxidation, and oxidative stress. To identify the putative protein regulators of UCP3, we performed yeast two-hybrid screens. Here we report that UCP3 interacted with HS-1 associated protein X-1 (Hax-1), an anti-apoptotic protein that was localized in the mitochondria, and is involved in cellular responses to Ca2+. The hydrophilic sequences within loop 2, and the matrix-localized hydrophilic domain of mouse UCP3, were necessary for binding to Hax-1 at the C-terminal domain, adjacent to the mitochondrial inner membrane. Interestingly, interaction of these proteins occurred in a calcium-dependent manner. Moreover, the NMR spectrum of the C-terminal domain of Hax-1 was dramatically changed by removal of Ca2+, suggesting that the C-terminal domain of Hax-1 underwent a Ca2+-induced conformational change. In the Ca2+-free state, the C-terminal Hax-1 tended to unfold, suggesting that Ca2+ binding may induce protein folding of the Hax-1 C-terminus. These results suggested that the UCP3-Hax-1 complex may regulate mitochondrial functional changes caused by mitochondrial Ca2+.
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