Phox homology domains specifically bind phosphatidylinositol phosphates
Phox homology domains specifically bind phosphatidylinositol phosphates
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DOI：
10.1021/bi0155100
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发表时间：
2001-07-31
期刊：
影响因子：
2.9
通讯作者：
Zhou, GW
中科院分区：
文献类型：
--
作者：
Song, X;Xu, W;Zhou, GW
通过结合磷脂酰肌醇的磷酸化衍生物（PtdIns）将特定的胞质蛋白募集到细胞内膜，控制诸如内吞作用、受调节的胞吐作用、细胞骨架组织和细胞信号传导等过程。蛋白质模块，如FVYE结构域和PH结构域，分别特异性结合PtdIns 3-磷酸（PtdIns-3-P）和聚磷酸肌醇，可以指导这种膜靶向。在这里，我们表明，两个代表性的Phox同源性（PX）域选择性地结合到特定的磷脂酰肌醇磷酸。Vam 7 p的PX结构域选择性结合PtdIns-3-P，而CPK PI-3激酶的PX结构域选择性结合PtdIns-4，5-P-2。相比之下，Vps 5 p的PX结构域显示不与测试的任何PtdInsP结合。此外，双突变体（Y 42 A/L48 Q）的PX结构域的Vam 7 p，据报道，导致空泡运输缺陷的酵母，具有显着降低的结合PtdIns-3-P的水平。这些数据表明，膜靶向功能的Vam 7 p PX结构域是基于其与PtdIns-3-P，类似于FYVE结构域的功能的能力。
The recruitment of specific cytosolic proteins to intracellular membranes through binding phosphorylated derivatives of phosphatidylinositol (PtdIns) controls such processes as endocytosis, regulated exocytosis, cytoskeletal organization, and cell signaling. Protein modules such as FVYE domains and PH domains that bind specifically to PtdIns 3-phosphate (PtdIns-3-P) and polyphosphoinositides, respectively, can direct such membrane targeting. Here we show that two representative Phox homology (PX) domains selectively bind to specific phosphatidylinositol phosphates. The PX domain of Vam7p selectively binds Ptdlns-3-P, while the PX domain of the CPK PI-3 kinase selectively binds PtdIns-4,5-P-2. In contrast, the PX domain of Vps5p displays no binding to any PtdInsPs that were tested. In addition, the double mutant (Y42A/L48Q) of the PX domain of Vam7p, reported to cause vacuolar trafficking defects in yeast, has a dramatically decreased level of binding to Ptdlns-3-P. These data reveal that the membrane targeting function of the Vam7p PX domain is based on its ability to associate with PtdIns-3-P, analogous to the function of FYVE domains.