A minimum structure of aminoglycosides that causes an initiation shift of trans-translation
A minimum structure of aminoglycosides that causes an initiation shift of trans-translation
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DOI：
10.1093/nar/gkh750
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发表时间：
2004-08-01
影响因子：
14.9
通讯作者：
Himeno, H
中科院分区：
文献类型：
--
作者：
Konno, T;Takahashi, T;Himeno, H
反式翻译是一种不寻常的翻译，其中转移信使RNA发挥双重功能-作为tRNA和mRNA-以缓解核糖体上停滞的翻译。已经表明，巴龙霉素是4，5-二取代氨基糖苷类的典型成员，在转译过程中导致tmRNA上的还原恢复点移动-1。为了解决这种新的效果的分子基础，我们研究了各种氨基糖苷类，可以结合周围的核糖体的小亚基的A位点在体外反式翻译的影响。妥布霉素和庆大霉素属于4，6-二取代的氨基糖苷类，具有与4，5-二取代的氨基糖苷类相似的环I和11，具有相似的作用。新霉胺，它只有环I和11，一个共同的结构共享的4，5-和4，6-二取代类的氨基糖苷类，是足以引起一个起始转变的反式翻译。相比之下，链霉素或潮霉素B，缺乏环1，没有引起起始位移。每种氨基糖苷类对转译的影响与最近的结构研究揭示的核糖体小亚基A位点构象变化的影响一致：巴龙霉素、妥布霉素和遗传霉素（归类为庆大霉素亚类），而不是链霉素和潮霉素B，从A位点螺旋中翻转出1492和1493处的两个保守腺嘌呤碱基。巴龙霉素的起始转变模式随着引入起始点上游区域的突变的变化而波动。
Trans-translation is an unusual translation in which transfer-messenger RNA plays a dual function-as a tRNA and an mRNA-to relieve the stalled translation on the ribosome. It has been shown that paromomycin, a typical member of a 4,5-disubstituted class of aminoglycosides, causes a shift of the translation-resuming point on the tmRNA by -1 during transtranslation. To address the molecular basis of this novel effect, we examined the effects of various aminoglycosides that can bind around the A site of the small subunit of the ribosome on trans-translation in vitro. Tobramycin and gentamicin, belonging to the 4,6-disubstituted class of aminoglycosides having rings I and 11 similar to those in the 4,5-disubstituted class, possess similar effects. Neamine, which has only rings I and 11, a common structure shared by 4,5- and 4,6-disubstituted classes of aminoglycosides, was sufficient to cause an initiation shift of trans-translation. In contrast, streptomycin or hygromycin B, lacking ring 1, did not cause an initiation shift. The effect of each aminoglycoside on transtranslation coincides with that on conformational change in the A site of the small subunit of the ribosome revealed by recent structural studies: paromomycin, tobramycin and geneticin which is categorized into the gentamicin subclass, but not streptomycin and hygromycin B, flip out two conserved adenine bases at 1492 and 1493 from the A site helix. The pattern of initiation shifts by paromomycin fluctuates with variation of mutations introduced into a region upstream of the initiation point.