Shine-Dalgarno interaction prevents incorporation of noncognate amino acids at the codon following the AUG
Shine-Dalgarno interaction prevents incorporation of noncognate amino acids at the codon following the AUG
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Shine-Dalgarno 相互作用可防止 AUG 之后的密码子处掺入非同源氨基酸
DOI：
10.1073/pnas.0801974105
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发表时间：
2008-08-05
影响因子：
11.1
通讯作者：
Nierhaus, Knud H.
中科院分区：
文献类型：
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作者：
Di Giacco, Viviana;Warquez, Viter;Nierhaus, Knud H.
在翻译过程中，通常在大约400个错配中只有一个错配会影响新生蛋白质的功能，因为只有化学上相似的近同源氨基酸被错配取代同源氨基酸。在选择过程中，由于核糖体E位点上存在一个tRNA，化学上不同的非同源氨基酸的有害错误掺入就被排除了。然而，在起始后直接选择第一个氨酰-tRNA，而不需要占据E-位点，即，当只有P-位点被起始tRNA填充时，因此应该是高度易错的。在这里，我们展示了细菌核糖体如何解决这个准确性问题：在没有Shine-Dalgarno（SD）序列的情况下，起始后A位点的第一个解码步骤非常容易出错，甚至导致非同源氨基酸的显著掺入。相反，当存在SD序列时，未观察到非同源氨基酸的掺入。这正是在延伸阶段在E位点存在同源tRNA的效果。这些研究结果表明，在起始阶段，SD相互作用功能补偿缺乏密码子-反密码子相互作用的E-网站，通过减少近同源氨基酸的错误掺入，并防止noncognate错误掺入。
During translation, usually only one in approximate to 400 misincorporations affects the function of a nascent protein, because only chemically similar near-cognate amino acids are misincorporated in place of the cognate one. The deleterious misincorporation of a chemically dissimilar noncognate amino acid during the selection process is precluded by the presence of a tRNA at the ribosomal E-site. However, the selection of first aminoacyl-tRNA, directly after initiation, occurs without an occupied E-site, i.e., when only the P-site is filled with the initiator tRNA and thus should be highly error-prone. Here, we show how bacterial ribosomes have solved this accuracy problem: In the absence of a Shine-Dalgarno (SD) sequence, the first decoding step at the A-site after initiation is extremely error-prone, even resulting in the significant incorporation of noncognate amino acids. In contrast, when a SD sequence is present, the incorporation of noncognate amino acids is not observed. This is precisely the effect that the presence of a cognate tRNA at the E-site has during the elongation phase. These findings suggest that during the initiation phase, the SD interaction functionally compensates for the lack of codon-anticodon interaction at the E-site by reducing the misincorporation of near-cognate amino acids and prevents noncognate misincorporation.