The PX domain as a novel phosphoinositide-binding module

The PX domain as a novel phosphoinositide-binding module
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DOI:
10.1006/bbrc.2001.5629
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发表时间:
2001-09-28
影响因子:
3.1
通讯作者:
Sumimoto, H
Sumimoto, H
中科院分区:
生物学4区
文献类型:
--
作者:
Ago, T;Takeya, R;Sumimoto, H

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phox(吞噬细胞氧化酶)同源(PX)结构域存在于哺乳动物phox蛋白p40(phox)和p47(phox)中。芽殖酵母中的极性建立蛋白Bem 1 p,以及多种参与膜运输的蛋白。我们发现p40(phox)和p47(phox)的PX结构域直接与磷酸肌醇结合:P40(phox)偏好Ptdlns(3)P,而p47(phox)偏好Ptdlns(4)P和Ptdlns(3,4)P-2。此外,Bem 1 p PX结构域还与Ptdlns(4)P相互作用。当P40(phox)PX结构域在HeLa细胞中表达为与绿色荧光蛋白的融合体时,它存在于Ptdlns(3)P富集的早期内体。此外,突变体P40(phox)PX携带的替换为Arg 105的赖氨酸在体外仅弱结合磷酸肌醇,并未能定位到早期内涵体。因此,PX结构域作为一种新的磷酸肌醇结合模块的功能,并可能参与靶向蛋白质的膜。(C)北京:科学出版社.
The phox (phagocyte oxidase) homology (PX) domain occurs in the mammalian phox proteins p40(phox) and p47(phox). the polarity establishment protein Bem1p in budding yeast, and a variety of proteins involved in membrane trafficking. Here we show that the PX domains of p40(phox) and p47(phox) directly bind to phosphoinositides: P40(phox) prefers Ptdlns(3)P, while p47(phox) does Ptdlns(4)P and Ptdlns(3,4)P-2. In addition, the Bem1p PX domain also interacts with Ptdlns(4)P. When the P40(phox) PX domain is expressed as a fusion to green fluorescent protein in HeLa cells, it exists at early endosomes where Ptdlns(3)P is enriched. Furthermore, a mutant P40(phox) PX carrying the substitution of Lys for Arg105 only weakly binds to phosphoinositides in vitro, and fails to locate to early endosomes. Thus the PX domain functions as a novel phosphoinositide-binding module and likely participates in targeting of proteins to membranes. (C) 2001 Academic Press.