PIP2-PDZ domain binding controls the association of syntenin with the plasma membrane
PIP2-PDZ domain binding controls the association of syntenin with the plasma membrane
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DOI：
10.1016/s1097-2765(02)00549-x
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发表时间：
2002-06-01
期刊：
影响因子：
16
通讯作者：
Gettemans, J
中科院分区：
文献类型：
--
作者：
Zimmermann, P;Meerschaert, K;Gettemans, J
PDZ蛋白组织多蛋白信号复合物。根据目前的观点，PDZ结构域参与蛋白质-蛋白质相互作用。在这里，我们证明了几种蛋白质的PDZ结构域结合磷脂酰肌醇4,5-二磷酸（PIP2）。syntenin与含pip2的脂质层的高亲和力结合需要该蛋白的两个PDZ结构域。竞争和诱变实验表明，该蛋白与PDZ结构域的PIP2结合位点重叠。覆盖实验表明，syntenin的两个PDZ结构域协同结合同源肽和PIP2。在活细胞上进行的实验证明了联质蛋白PDZ结构域的质膜结合具有pip2依赖和肽依赖两种模式。这些观察结果表明，磷肌苷浓度的局部变化控制了PDZ蛋白与其质膜靶受体的结合。
PDZ proteins organize multiprotein signaling complexes. According to current views, PDZ domains engage in protein-protein interactions. Here we show that the PDZ domains of several proteins bind phosphatidylinositol 4,5-bisphosphate (PIP2). High-affinity binding of syntenin to PIP2-containing lipid layers requires both PDZ domains of this protein. Competition and mutagenesis experiments reveal that the protein and the PIP2 binding sites in the PDZ domains overlap. Overlay assays indicate that the two PDZ domains of syntenin cooperate in binding to cognate peptides and PIP2. Experiments on living cells demonstrate PIP2-dependent and peptide-dependent modes of plasma membrane association of the PDZ domains of syntenin. These observations suggest that local changes in phosphoinositide concentration control the association of PDZ proteins with their target receptors at the plasma membrane.