Structural insights into eRF3 and stop codon recognition by eRF1
Structural insights into eRF3 and stop codon recognition by eRF1
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DOI：
10.1101/gad.1770109
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发表时间：
2009-05-01
影响因子：
10.5
通讯作者：
Song, Haiwei
中科院分区：
文献类型：
--
作者：
Cheng, Zhihong;Saito, Kazuki;Song, Haiwei
真核翻译终止是由两个相互作用的释放因子ERF1和ERF3介导的，ERF1和ERF3起作用，以确保有效的停止密码子识别和快速多肽释放。人和精神分裂症的晶体结构与ERF3缺乏GTPase结构域的复合物中的全长ERF1的全长ERF1揭示了这两个因素之间的相互作用的细节以及ERF1与ERF3结合后发生的ERF1明显构象变化的细节，导致ERF1导致ERF1与TRNA分子相似。 ERF1/ERF3/GTP复合物的小角度X射线散射分析表明，ERF1的M域接触ERF3的GTPase域。一致地，预计将与ERF3的开关区密切接触的Arg192突变揭示了其对ERF1对ERF3 GTPase活性的刺激作用的重要作用。用作结晶添加剂的ATP分子在ERF1推定的解码区域结合。对ATP结合位点的突变分析阐明了ERF1终止密码子识别的机理。
Eukaryotic translation termination is mediated by two interacting release factors, eRF1 and eRF3, which act cooperatively to ensure efficient stop codon recognition and fast polypeptide release. The crystal structures of human and Schizosaccharomyces pombe full-length eRF1 in complex with eRF3 lacking the GTPase domain revealed details of the interaction between these two factors and marked conformational changes in eRF1 that occur upon binding to eRF3, leading eRF1 to resemble a tRNA molecule. Small-angle X-ray scattering analysis of the eRF1/eRF3/GTP complex suggested that eRF1's M domain contacts eRF3's GTPase domain. Consistently, mutation of Arg192, which is predicted to come in close contact with the switch regions of eRF3, revealed its important role for eRF1's stimulatory effect on eRF3's GTPase activity. An ATP molecule used as a crystallization additive was bound in eRF1's putative decoding area. Mutational analysis of the ATP-binding site shed light on the mechanism of stop codon recognition by eRF1.