Structural basis for the selection of glycosylated substrates by SCFFbs1 ubiquitin ligase
Structural basis for the selection of glycosylated substrates by SCFFbs1 ubiquitin ligase
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DOI：
10.1073/pnas.0610312104
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发表时间：
2007-04-03
影响因子：
11.1
通讯作者：
Tanaka, Keiji
中科院分区：
文献类型：
--
作者：
Mizushima, Tsunehiro;Yoshida, Yukiko;Tanaka, Keiji
泛素连接酶复合物SCFFbs 1参与了内质网相关的降解途径，它有助于糖蛋白的泛素化。在SCF泛素连接酶中，一系列不同的F-box蛋白赋予底物特异性。Fbs 1/Fbx 2是F-box蛋白家族的成员，识别高甘露寡糖。为了阐明SCFFbs 1功能的结构基础，我们确定了Skp 1-Fbs 1复合物的晶体结构和Fbs 1-糖蛋白复合物的糖结合结构域（SBD）。由结构所指示的机制模型似乎在SCIF泛素连接酶之间是很保守的。SBD-糖蛋白复合物的结构表明，SBD主要识别Man（3）GlcNAc（2），从而解释了该酶对各种糖蛋白的广泛活性。Skp 1-Fbs 1复合物的两种晶体结构的比较揭示了F-盒和SBD结构域之间的连接片段的相对运动，这可能是复合物识别不同受体赖氨酸残基用于泛素化的能力的基础。
The ubiquitin ligase complex SCFFbs1, which contributes to the ubiquitination of glycoproteins, is involved in the endoplasmic reticulum-associated degradation pathway. In SCF ubiquitin ligases, a diverse array of F-box proteins confers substrate specificity. Fbs1/Fbx2, a member of the F-box protein family, recognizes high-mannose oligosaccharides. To elucidate the structural basis of SCFFbs1 function, we determined the crystal structures of the Skp1-Fbs1 complex and the sugar-binding domain (SBD) of the Fbs1-glycoprotein complex. The mechanistic model indicated by the structures appears to be well conserved among the SCIF ubiquitin ligases. The structure of the SBD-glycoprotein complex indicates that the SBD primarily recognizes Man(3)GlcNAc(2), thereby explaining the broad activity of the enzyme against various glycoproteins. Comparison of two crystal structures of the Skp1-Fbs1 complex revealed the relative motion of a linker segment between the F-box and the SBD domains, which might underlie the ability of the complex to recognize different acceptor lysine residues for ubiquitination.