Mitochondrial alterations induced by the p13II protein of human T-cell leukemia virus type 1 -: Critical role of arginine residues
Mitochondrial alterations induced by the p13II protein of human T-cell leukemia virus type 1 -: Critical role of arginine residues
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DOI：
10.1074/jbc.m203023200
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发表时间：
2002-09-13
影响因子：
4.8
通讯作者：
Ciminale, V
中科院分区：
文献类型：
--
作者：
D'Agostino, DM;Ranzato, L;Ciminale, V
人类t细胞白血病病毒1型编码一些功能不明确的“辅助”蛋白；其中一种蛋白质p13（II）以线粒体为靶点，破坏线粒体形态。本研究通过(i)确定p13（II）的亚线粒体定位和改变线粒体形态所需的序列，以及（II）评估跨越残基9-41 （p13(9-41)）的合成肽的生物物理和生物学特性，其中包括蛋白质的两亲性线粒体靶向序列，来揭示p13（II）的功能。P13（9-41）在胶束环境中折叠成a螺旋。免疫金标记表明全长p13（II）聚集在线粒体内膜内。p13（9-41）通过增加细胞膜对小阳离子（Na+, K+）的通透性，并从Ca2+预载的线粒体中释放Ca2+，诱导离体线粒体的能量依赖性肿胀。这些作用以及全长p13（II）改变细胞线粒体形态的能力需要四种精氨酸的存在，形成靶向信号的带电面。p13（9-41）的线粒体作用对环孢素A不敏感，这表明全长p13（II）可能通过渗透性过渡与孔无关的机制改变线粒体的通透性，从而将其与人类免疫缺陷病毒1型和乙型肝炎病毒的线粒体蛋白Vpr和X区分开来。
Human T-cell leukemia virus type 1 encodes a number of "accessory" proteins of unclear function; one of these proteins, p13(II), is targeted to mitochondria and disrupts mitochondrial morphology. The present study was undertaken to unravel the function of p13(II) through (i) determination of its submitochondrial localization and sequences required to alter mitochondrial morphology and (ii) an assessment of the biophysical and biological properties of synthetic peptides spanning residues 9-41 (p13(9-41)), which include the amphipathic mitochondrial-targeting sequence of the protein. p13(9-41) folded into an a helix in micellar environments. Fractionation an immunogold labeling indicated that full-length p13(II) accumulates in the inner mitochondrial membrane. p13(9-41) induced energy-dependent swelling of isolated mitochondria by increasing inner membrane permeability to small cations (Na+, K+) and released Ca2+ from Ca2+-preloaded mitochondria. These effects as well as the ability of full-length p13(II) to alter mitochondrial morphology in cells required the presence of four arginines, forming the charged face of the targeting signal. The mitochondrial effects of p13(9-41) were insensitive to cyclosporin A, suggesting that full-length p13(II) might alter mitochondrial permeability through a permeability transition pore-independent mechanism, thus distinguishing it from the mitochondrial proteins Vpr and X of human immunodeficiency virus type 1 and hepatitis B virus, respectively.