Structural basis of protein arginine rhamnosylation by glycosyltransferase EarP
Structural basis of protein arginine rhamnosylation by glycosyltransferase EarP
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DOI：
10.1038/s41589-018-0002-y
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发表时间：
2018-04-01
影响因子：
14.8
通讯作者：
Yanagisawa, Tatsuo
中科院分区：
文献类型：
--
作者：
Sengoku, Toru;Suzuki, Takehiro;Yanagisawa, Tatsuo
蛋白质糖基化调节许多细胞过程。许多具有广泛底物特异性的糖基转移酶已被结构表征。一种新的倒置糖基转移酶EarP特异性地将鼠李糖从dtdp - β - l -鼠李糖转移到细菌翻译伸长因子P （EF-P）的Arg32上，以激活其功能。在这里，我们报告脑膜炎奈瑟菌EarP的结晶学研究。EarP结构包含两个串联的Rossmann-fold结构域，这将EarP归类于糖基转移酶超家族b中。与其他具有结构特征的蛋白糖基转移酶相比，EarP通过许多相互作用结合EF-P结构域I的整个β -sheet结构，特异性识别其保守残基。因此Arg32恰好位于活性位点，并引起EarP保守的dtdp - β - l -鼠李糖结合环的结构变化。EarP应通过S(N)2反应进行鼠李糖基化，以Asp20为一般碱。Arg32结合和伴随的EarP结构变化可能导致鼠李糖环构象的变化。
Protein glycosylation regulates many cellular processes. Numerous glycosyltransferases with broad substrate specificities have been structurally characterized. A novel inverting glycosyltransferase, EarP, specifically transfers rhamnose from dTDP-beta-L-rhamnose to Arg32 of bacterial translation elongation factor P (EF-P) to activate its function. Here we report a crystallographic study of Neisseria meningitidis EarP. The EarP structure contains two tandem Rossmann-fold domains, which classifies EarP in glycosyltransferase superfamily B. In contrast to other structurally characterized protein glycosyltransferases, EarP binds the entire beta-sheet structure of EF-P domain I through numerous interactions that specifically recognize its conserved residues. Thus Arg32 is properly located at the active site, and causes structural change in a conserved dTDP-beta-L-rhamnose-binding loop of EarP. Rhamnosylation by EarP should occur via an S(N)2 reaction, with Asp20 as the general base. The Arg32 binding and accompanying structural change of EarP may induce a change in the rhamnose-ring conformation suitable for the reaction.