Role of forefinger and thumb loops in production of Ψ54 and Ψ55 in tRNAs by archaeal Pus10.
Role of forefinger and thumb loops in production of Ψ54 and Ψ55 in tRNAs by archaeal Pus10.
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DOI：
10.1261/rna.039230.113
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发表时间：
2013-09
期刊：
影响因子：
--
通讯作者：
Gupta R
中科院分区：
文献类型：
--
作者：
Joardar A;Jana S;Fitzek E;Gurha P;Majumder M;Chatterjee K;Geisler M;Gupta R
通过结构模型和一系列突变的比较，我们确定了古细菌Pus10的食指环和Arg和Tyr残基是其tRNA Ψ54活性的关键决定因素，而Leu残基和催化Asp是Ψ54和Ψ55活性的关键决定因素。我们认为，古细菌Pus10使用两种不同的机制来识别和结合底物尿苷，并且这两种机制有一些共同的特点。伪尿嘧啶（Ψ）存在于rna结构和功能的重要区域。已鉴定出6个Ψ合成酶家族，TruA、TruB、TruD、RsuA、RluA和Pus10。Pus10存在于古生菌和真核菌中。虽然大多数古细菌Pus10同时产生tRNA Ψ54和Ψ55，但有些只产生Ψ55。有趣的是，人类PUS10与细胞凋亡、克罗恩病和乳糜泻有关。基于人类Pus10晶体结构的古细菌Pus10蛋白同源性模型显示，所有这些Pus10蛋白在结构上都存在细微的差异。这些观察结果表明，同源蛋白的结构变化可能导致其功能的丧失、获得或改变，因此有必要研究这些蛋白的结构-功能关系。通过结构模型和一系列突变的比较，我们确定了食指环（类似于RluA）和古细菌Pus10的Arg和Tyr残基是其Ψ54活性的关键决定因素，而不是Ψ55活性的关键决定因素。我们还发现，亮氨酸残基，除了催化Asp，是必不可少的这两个活性。由于rRNA和tRNA Ψ合成酶的RluA活性都需要食指环，但只有tRNA Ψ54的Pus10活性需要食指环，因此古细菌Pus10蛋白必须使用不同的机制来识别Ψ55活性。我们提出古细菌Pus10使用两种不同的机制来识别和结合底物尿苷。然而，由于我们没有观察到任何仅影响Ψ55活性的突变，因此古细菌Pus10活性的两种机制必须具有一些共同的特征。
Using comparison of structural models and a series of mutations, forefinger loop and an Arg and a Tyr residue of archaeal Pus10 have been determined as critical determinants for its tRNA Ψ54 activity, while a Leu residue and the catalytic Asp are essential for both Ψ54 and Ψ55 activities. It is proposed that archaeal Pus10 uses two distinct mechanisms for substrate uridine recognition and binding, and the two mechanisms share some common features. Pseudouridines (Ψ) are found in structurally and functionally important regions of RNAs. Six families of Ψ synthases, TruA, TruB, TruD, RsuA, RluA, and Pus10 have been identified. Pus10 is present in Archaea and Eukarya. While most archaeal Pus10 produce both tRNA Ψ54 and Ψ55, some produce only Ψ55. Interestingly, human PUS10 has been implicated in apoptosis and Crohn’s and Celiac diseases. Homology models of archaeal Pus10 proteins based on the crystal structure of human PUS10 reveal that there are subtle structural differences in all of these Pus10 proteins. These observations suggest that structural changes in homologous proteins may lead to loss, gain, or change of their functions, warranting the need to study the structure-function relationship of these proteins. Using comparison of structural models and a series of mutations, we identified forefinger loop (reminiscent of that of RluA) and an Arg and a Tyr residue of archaeal Pus10 as critical determinants for its Ψ54, but not for its Ψ55 activity. We also found that a Leu residue, in addition to the catalytic Asp, is essential for both activities. Since forefinger loop is needed for both rRNA and tRNA Ψ synthase activities of RluA, but only for tRNA Ψ54 activity of Pus10, archaeal Pus10 proteins must use a different mechanism of recognition for Ψ55 activity. We propose that archaeal Pus10 uses two distinct mechanisms for substrate uridine recognition and binding. However, since we did not observe any mutation that affected only Ψ55 activity, both mechanisms for archaeal Pus10 activities must share some common features.
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