Structural insights into the PIP2 recognition by syntenin-1 PDZ domain.
Structural insights into the PIP2 recognition by syntenin-1 PDZ domain.
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DOI：
10.1016/j.bbrc.2007.11.138
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发表时间：
2008-02
影响因子：
3.1
通讯作者：
T. Sugi;T. Oyama;K. Morikawa;H. Jingami
中科院分区：
文献类型：
--
作者：
T. Sugi;T. Oyama;K. Morikawa;H. Jingami
C末端配体与PDZ结构域结合的脂类调节机制尚不完全清楚，尽管它们在亚细胞组织中发挥作用。在这里，我们提供了对PDZ结构域的磷脂酰肌醇4，5-二磷酸(PIP2)识别模式的结构见解，这是从磷酸结合的PDZ结构域的晶体结构中揭示的。两个相邻的磷酸根离子与α2螺旋氨基末端附近的碱性残基结合，反映了PIP2的两个磷酸基团的相互作用方式。基于观察到的两个磷酸分子在PDZ结构域中的位置，我们建立了PIP2与众所周知的PIP2结合蛋白Syntenin-1的PDZ结构域的对接模型。这一模型表明，PIP2的疏水甘油基团可以与PDZ结构域的配体结合槽接触。这些结构特征很好地解释了以前报道的PIP2介导的PDZ配体结合调节的生物学现象。
Lipid-mediated regulatory mechanism of the C-terminal ligand binding to PDZ domains is not fully understood, despite their roles in subcellular organization. Here, we provide structural insights into the phosphatidylinositol 4,5-bisphosphate (PIP2) recognition mode of a PDZ domain, as revealed from the crystal structure of the phosphate-bound PDZ domain. Two adjacent phosphate ions bind to the basic residues close to the amino terminus of the α2 helix in the Tamalin PDZ domain, reflecting an interaction mode of the two phosphate groups of PIP2. Based on the observed location of the two phosphate molecules within the PDZ domain, we built the docking model of PIP2with the PDZ domain of the well-known PIP2-binding protein, syntenin-1. This model suggests that the hydrophobic diacylglycerol group of PIP2could contact the ligand-binding groove of the PDZ domain. These structural features well explain biological phenomena, which were previously reported for the PIP2-mediated PDZ ligand-binding regulation.