Structure of Osh3 Reveals a Conserved Mode of Phosphoinositide Binding in Oxysterol-Binding Proteins
Structure of Osh3 Reveals a Conserved Mode of Phosphoinositide Binding in Oxysterol-Binding Proteins
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DOI：
10.1016/j.str.2013.05.007
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发表时间：
2013-07-02
期刊：
影响因子：
5.7
通讯作者：
Im, Young Jun
中科院分区：
文献类型：
--
作者：
Tong, Junsen;Yang, Huiseon;Im, Young Jun
氧化固醇结合蛋白（OSBP）相关蛋白（ORP）是从酵母到人类的保守蛋白，参与脂质稳态的调节和信号通路。酿酒酵母有七个ORF（Osh 1-Osh 7），它们共享一个未知的基本功能。在这里，我们报告了1.5-2.3埃结构的PH结构域和ORD（OSBP相关结构域）的酵母Osh 3在apo形式或与磷脂酰肌醇4-磷酸（PI[4]P）的复合物。Osh 3通过ORD通道中高度保守的残基识别PI（4）P，而由于狭窄的疏水通道，Osh 3缺乏甾醇结合。酵母互补试验表明，PI（4）P与PH和ORD的结合对功能是必不可少的。这项研究表明，在所有ORP同系物的统一功能是结合PI（4）P的ORD和甾醇结合是额外的某些同系物。全长Osh 3的结构建模与Osh 3是膜接触位点中的脂质转移蛋白或调节剂的概念一致。
The oxysterol-binding protein (OSBP)-related proteins (ORPs) are conserved from yeast to humans, and implicated in the regulation of lipid homeostasis and in signaling pathways. Saccharomyces cerevisiae has seven ORPs (Osh1-Osh7) that share one unknown essential function. Here, we report the 1.5-2.3 angstrom structures of the PH domain and ORD (OSBP-related domain) of yeast Osh3 in apo-form or in complex with phosphatidylinositol 4-phosphate (PI[4]P). Osh3 recognizes PI(4)P by the highly conserved residues in the tunnel of ORD whereas it lacks sterol binding due to the narrow hydrophobic tunnel. Yeast complementation tests suggest that PI(4)P binding to PH and ORD is essential for function. This study suggests that the unifying feature in all ORP homologs is the binding of PI(4)P to ORD and sterol binding is additional to certain homologs. Structural modeling of full-length Osh3 is consistent with the concept that Osh3 is a lipid transfer protein or regulator in membrane contact sites.