Structural basis for membrane targeting by the MVB12-associated β-prism domain of the human ESCRT-I MVB12 subunit
Structural basis for membrane targeting by the MVB12-associated β-prism domain of the human ESCRT-I MVB12 subunit
复制标题
DOI：
10.1073/pnas.1117597109
复制
发表时间：
2012-02-07
影响因子：
11.1
通讯作者：
Hurley, James H.
中科院分区：
文献类型：
--
作者：
Boura, Evzen;Hurley, James H.
MVB 12相关β-棱镜（MABP）域被预测发生在一组不同的膜相关的细菌和真核生物蛋白，但它们的存在，结构和生化特性尚未实验表征。在这里，我们发现，MABP结构域的MVB 12 A和B亚基的ESCRT-I的功能模块，结合在体外含有酸性脂质体依赖于负电荷密度。MABP结构域能够自主定位于亚细胞点和质膜。MVB 12 B MABP结构域的1.3埃原子分辨率晶体结构揭示了β-棱柱折叠、疏水膜锚定环和正电性磷酸肌醇结合补丁。基本的补丁是开放的，这解释了它如何感知负电荷密度，但缺乏立体选择性。这些观察结果表明，ESCRT-I如何能够作为酸性磷脂和蛋白质配体的符合检测器，使其能够在蛋白质内体转运和胞质分裂以及质膜上的病毒出芽中发挥作用。
MVB12-associated beta-prism (MABP) domains are predicted to occur in a diverse set of membrane-associated bacterial and eukaryotic proteins, but their existence, structure, and biochemical properties have not been characterized experimentally. Here, we find that the MABP domains of the MVB12A and B subunits of ESCRT-I are functional modules that bind in vitro to liposomes containing acidic lipids depending on negative charge density. The MABP domain is capable of autonomously localizing to subcellular puncta and to the plasma membrane. The 1.3-angstrom atomic resolution crystal structure of the MVB12B MABP domain reveals a beta-prism fold, a hydrophobic membrane-anchoring loop, and an electropositive phosphoinositide-binding patch. The basic patch is open, which explains how it senses negative charge density but lacks stereo-selectivity. These observations show how ESCRT-I could act as a coincidence detector for acidic phospholipids and protein ligands, enabling it to function both in protein transport at endosomes and in cytokinesis and viral budding at the plasma membrane.