Dual-mode recognition of noncanonical tRNAsSer by seryl-tRNA synthetase in mammalian mitochondria
Dual-mode recognition of noncanonical tRNAsSer by seryl-tRNA synthetase in mammalian mitochondria
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DOI：
10.1038/sj.emboj.7600811
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发表时间：
2005-10-05
期刊：
影响因子：
11.4
通讯作者：
Watanabe, K
中科院分区：
文献类型：
--
作者：
Chimnaronk, S;Jeppesen, MG;Watanabe, K
后生动物线粒体（mt）tRNA Ser的二级结构明显偏离典型的三叶草结构范式;特别地，对应于AGY密码子的tRNA（GCU）（Ser（Y = U和C）是高度截短的并且本质上缺失整个二氢尿苷臂。mt丝氨酸同种受体都不具有伸长的可变臂，其是丝氨酰-tRNA合成酶（SerRS）识别的通用标志。在这里，我们报告的晶体结构的哺乳动物线粒体SerRS从牛在复杂的丝氨酰腺苷酸在1.65埃的原子分辨率。耦合结构信息与tRNA对接模型和诱变研究，我们已经解开的关键要素，建立tRNA结合特异性，不同于所有其他已知的细菌和真核生物系统，是在两端的特征性延伸，以及一些基本残基驻留在氨基末端螺旋臂的mt SerRS。我们的数据进一步揭示了一个前所未有的双模式识别机制，用于区分两个不同的“奇异”的mt tRNA（Ser）的相互作用位点的替代组合。
The secondary structures of metazoan mitochondrial (mt) tRNAs Ser deviate markedly from the paradigm of the canonical cloverleaf structure; particularly, tRNA(GCU)(Ser) corresponding to the AGY codon ( Y = U and C) is highly truncated and intrinsically missing the entire dihydrouridine arm. None of the mt serine isoacceptors possesses the elongated variable arm, which is the universal landmark for recognition by seryl-tRNA synthetase (SerRS). Here, we report the crystal structure of mammalian mt SerRS from Bos taurus in complex with seryl adenylate at an atomic resolution of 1.65 angstrom. Coupling structural information with a tRNA-docking model and the mutagenesis studies, we have unraveled the key elements that establish tRNA binding specificity, differ from all other known bacterial and eukaryotic systems, are the characteristic extensions in both extremities, as well as a few basic residues residing in the amino-terminal helical arm of mt SerRS. Our data further uncover an unprecedented mechanism of a dual-mode recognition employed to discriminate two distinct `bizarre' mt tRNAs(Ser) by alternative combination of interaction sites.