Pactamycin resistance mutations in functional sites of 16S rRNA
Pactamycin resistance mutations in functional sites of 16S rRNA
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DOI：
10.1006/jmbi.1997.1387
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发表时间：
1997-11-21
影响因子：
5.6
通讯作者：
Mankin, AS
中科院分区：
文献类型：
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作者：
Mankin, AS
古细菌 Halobacter halobium 的突变体对通用翻译抑制剂 pactamycin 具有抗性，已被分离出来。帕大霉素抗性与 H. halobiun 单 rRNA 操纵子的 16 S rRNA 基因突变的存在相关。在赤霉素抗性细胞中发现了三种类型的突变，A694G、C795U 和 C796U（大肠杆菌 16 S rRNA 计数），它们在 rRNA 一级结构中位置较远，但在三维结构中可能彼此相邻。帕克霉素抗性突变要么重叠（C795U），要么位于大肠杆菌和卤杆菌 16 S rRNA 中受药物保护的核苷酸附近，表明相应的 rRNA 位点可能直接参与帕克霉素结合。核糖体功能并未受到 C795 突变（受 P 位点结合 tRNA 保护的位置之一）或 A694 和 C796 突变（与受 tRNA 保护的核苷酸相邻）的显着影响，这表明 C795 和 G693 的 tRNA 依赖性保护是由 P 位点结合 tRNA 诱导的核糖体构象变化来解释的。提出了一种新的 pactamycin 作用模式，表明 pactamycin 限制 16 S rRNA 中的结构转变，防止核糖体采用 tRNA 结合诱导的功能构象。 (C) 1997 学术出版社有限公司。
Mutants of an archaeon Halobacterium halobium, resistant to the universal inhibitor of translation, pactamycin, were isolated. Pactamycin resistance correlated with the presence of mutations in the 16 S rRNA gene of H. halobiun single rRNA operon. Three types of mutations were found in pactamycin resistant cells, A694G, C795U and C796U (Escherichia coli 16 S rRNA numeration) located distantly in rRNA primary structure but probably neighboring each other in the three-dimensional structure. Pactamycin resistance mutations either overlapped (C795U) or were located in the immediate vicinity of nucleotides protected by the drug in E. coli and H. halobium 16 S rRNA indicating that corresponding rRNA sites might be directly involved in pactamycin binding. Ribosomal functions were not affected significantly either by mutation of C795 (one of the positions protected by the P-site-bound tRNA), or by mutations of A694 and C796 (which neighbor nucleotides protected by tRNA) suggesting that tRNA-dependent protections of C795 and G693 are explained by a conformational change in the ribosome induced by the P-site-bound tRNA. A novel mode of pactamycin action is proposed suggesting that pactamycin restricts structural transitions in 16 S rRNA preventing the ribosome from adopting a functional conformation induced by tRNA binding. (C) 1997 Academic Press Limited.