Structure of the PTEN-like region of auxilin, a detector of clathrin-coated vesicle budding.

Structure of the PTEN-like region of auxilin, a detector of clathrin-coated vesicle budding.
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DOI:
10.1016/j.str.2010.06.016
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发表时间:
2010-09-08
期刊:
影响因子:
5.7
通讯作者:
Kirchhausen, Tomas
Kirchhausen, Tomas
中科院分区:
生物学2区
文献类型:
--
作者:
Guan, Rong;Han, Dai;Harrison, Stephen C.;Kirchhausen, Tomas

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一种含有J结构域的蛋白质,将Hsc70未包被的ATP酶募集到新出芽的网格蛋白包被的囊泡。生长素到达的时间决定了只有在网格蛋白晶格完全组装后和膜分裂完成后才开始脱壳。白蛋白具有类似于PTEN的区域,其为PI3P磷酸酶。我们已经确定了牛生长素1这一区域的晶体结构,它确实与PTEN非常相似。P环结构的变化是磷酸酶活性缺乏的原因。磷脂酰肌醇磷酸的列入大大提高了脂质体结合野生型生长素,但不是由各种突变体轴承环的C2结构域的变化。几乎所有这些突变也阻止了生长素向新出芽的被膜囊泡的募集。我们提出了一个特定的几何生长素协会与膜双层,并讨论了该模型的影响,生长素检测分离的囊泡从其母膜的机制。
Auxilin, a J-domain containing protein, recruits the Hsc70 uncoating ATPase to newly budded clathrin-coated vesicles. The timing of auxilin arrival determines that uncoating will commence only after the clathrin lattice has fully assembled and after membrane fission is complete. Auxilin has a region resembling PTEN, a PI3P phosphatase. We have determined the crystal structure of this region of bovine auxilin 1; it indeed resembles PTEN closely. A change in the structure of the P-loop accounts for the lack of phosphatase activity. Inclusion of phosphatidylinositol phosphates substantially enhances liposome binding by wild-type auxilin, but not by various mutants bearing changes in loops of the C2 domain. Nearly all these mutations also prevent recruitment of auxilin to newly budded coated vesicles. We propose a specific geometry for auxilin association with a membrane bilayer and discuss implications of this model for the mechanism by which auxilin detects separation of a vesicle from its parent membrane.
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