Structural Conservation of the Two Phosphoinositide-Binding Sites in WIPI Proteins
Structural Conservation of the Two Phosphoinositide-Binding Sites in WIPI Proteins
复制标题
WIPI 蛋白中两个磷酸肌醇结合位点的结构保守
DOI：
10.1016/j.jmb.2019.02.019
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发表时间：
2019-03-29
影响因子：
5.6
通讯作者：
Feng, Wei
中科院分区：
文献类型：
--
作者：
Liang, Ruobing;Ren, Jinqi;Feng, Wei
Wiri蛋白是哺乳动物中的PROPPIN家族成员，与磷脂酰肌醇结合，在自噬小体的生物发生中发挥重要作用。此前已在酵母PROPPIN HSV2中描述了两个磷脂酰肌醇结合位点，但在哺乳动物Wipi蛋白中仍有待确定。在这里，我们鉴定了四种人类WIPI蛋白(WIPI1-4)，并解决了WIPI3的结构问题。WIPI蛋白可以与PI(3)P和PI(3，5)P-2结合，并采用传统的七叶片β-螺旋桨折叠。WIPI3的结构表明，WIPI蛋白还含有两个嵌入在叶片5和6上的识别肌醇磷脂的位点，与HSV2相似。结构比较进一步证明，PROPPIN蛋白中的两个保守的肌醇磷脂结合位点并不完全相同，但本质上倾向于识别不同类型的肌醇磷脂。这项工作为支持WIPI蛋白中两个肌醇磷脂结合位点的保守性提供了结构证据，并揭示了每个位点潜在的肌醇磷脂结合选择性。(C)2019爱思唯尔有限公司。保留所有权利。
WIRI proteins are mammalian PROPPIN family members that bind to phosphoinositides and play prominent roles in autophagosome biogenesis. Two phosphoinositide-binding sites were previously described in yeast PROPPIN Hsv2 but remain to be determined in mammalian WIPI proteins. Here, we characterized four human WIPI proteins (WIPI1-4) and solved the structure of WIPI3. WIPI proteins can bind to PI(3)P and PI(3,5)P-2 and adopt a conventional seven-bladed beta-propeller fold. The structure of WIPI3 revealed that WIPI proteins also contain two sites embedded in blades 5 and 6 for recognizing phosphoinositides, resembling that in Hsv2. Structural comparison further demonstrated that the two conserved phosphoinositide-binding sites in PROPPIN proteins are not identical but intrinsically tend to recognize different types of phosphoinositides. This work provides the structural evidence to support the conservation of the two phosphoinositide-binding sites in WIPI proteins and also uncovers the potential phosphoinositide-binding selectivity for each site. (C) 2019 Elsevier Ltd. All rights reserved.