Dissecting the ribosomal inhibition mechanisms of edeine and pactamycin: The universally conserved residues G693 and C795 regulate P-site RNA binding
Dissecting the ribosomal inhibition mechanisms of edeine and pactamycin: The universally conserved residues G693 and C795 regulate P-site RNA binding
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DOI：
10.1016/s1097-2765(04)00002-4
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发表时间：
2004-01-16
期刊：
影响因子：
16
通讯作者：
Nierhaus, KH
中科院分区：
文献类型：
--
作者：
Dinos, G;Wilson, DN;Nierhaus, KH
结合核糖体30S亚基的通用翻译起始抑制剂edeine和pactamycin的晶体结构表明，edeine诱导构成pactamycin结合位点的残基G693:C795碱基配对。在这里，我们发现添加乙胺形成的碱基对通过阻止密码子-反密码子相互作用抑制tRNA与P位点的结合，而添加重新破坏碱基对的pactamycin可以缓解这种抑制。此外，乙胺在A位点诱导翻译误读，其水平与经典误读抗生素链霉素诱导的水平相当。pactamycin在残基G693和C795之间的结合强烈抑制易位，具有令人惊讶的tRNA特异性，但对翻译起始没有影响，这表明对这种抗生素的重新分类是必要的。综上所述，这些结果表明普遍保守的G693:C795残基调控tRNA在核糖体P位点的结合并影响易位效率。
The crystal structures of the universal translation-initiation inhibitors edeine and pactamycin bound to ribosomal 30S subunit have revealed that edeine induces base pairing of G693:C795, residues that constitute the pactamycin binding site. Here, we show that base pair formation by addition of edeine inhibits tRNA binding to the P site by preventing codon-anticodon interaction and that addition of pactamycin, which re-breaks the base pair, can relieve this inhibition. In addition, edeine induces translational misreading in the A site, at levels comparable to those induced by the classic misreading antibiotic streptomycin. Binding of pactamycin between residues G693 and C795 strongly inhibits translocation with a surprising tRNA specificity but has no effect on translation initiation, suggesting that reclassification of this antibiotic is necessary. Collectively, these results suggest that the universally conserved G693:C795 residues regulate tRNA binding at the P site of the ribosome and influence translocation efficiency.