Molecular Dynamics Simulations Suggest a Non-Doublet Decoding Model of -1 Frameshifting by tRNASer3
Molecular Dynamics Simulations Suggest a Non-Doublet Decoding Model of -1 Frameshifting by tRNASer3
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DOI：
10.3390/biom9110745
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发表时间：
2019-11-01
期刊：
影响因子：
5.5
通讯作者：
Flores, Samuel Coulbourn
中科院分区：
文献类型：
--
作者：
Caulfield, Thomas;Coban, Matt;Flores, Samuel Coulbourn
核糖体中的框内解码通过三个mRNA密码子碱基（三联体）与tRNA中的反密码子碱基三联体的规范或摆动沃森-克里克配对发生。来自三联体-三联体相互作用的结果可以导致移码，这意味着下游mRNA密码子然后在不同的寄存器中读取。有许多机制可以引起框架转换，但大多数机制还没有得到充分的理解。一个先前提出的机制是双重解码，其中只有密码子碱基1和2被反密码子碱基34和35读取，这将导致-1移码。在大肠在大肠杆菌中，tRNA（GCU）（Ser 3）能诱导丙氨酸（GCA）密码子的-1移码。双重解码模型的逻辑是，Ala密码子的GC可以与tRNA（Ser 3 '）的GC配对，留下第三个反密码子残基U36不与mRNA相互作用。在该模型下，U36 C突变仍然会诱导-1移码，但实验反驳了这一点。我们对野生型tRNA（Ser 3）以及U36 C突变体进行全原子模拟。我们的模拟揭示了反密码子的U36和密码子的G1之间的氢键。U36 C突变体不能产生这种相互作用，因为它缺乏氢键供体H3。因此，模拟表明了一种新的，非双重解码机制的-1移码的tRNA（Ser 3）在Ala密码子。
In-frame decoding in the ribosome occurs through canonical or wobble Watson-Crick pairing of three mRNA codon bases (a triplet) with a triplet of anticodon bases in tRNA. Departures from the triplet-triplet interaction can result in frameshifting, meaning downstream mRNA codons are then read in a different register. There are many mechanisms to induce frameshifting, and most are insufficiently understood. One previously proposed mechanism is doublet decoding, in which only codon bases 1 and 2 are read by anticodon bases 34 and 35, which would lead to -1 frameshifting. In E. coli, tRNA(GCU)(Ser3) can induce -1 frameshifting at alanine (GCA) codons. The logic of the doublet decoding model is that the Ala codon's GC could pair with the tRNA(Ser3 ')s GC, leaving the third anticodon residue U36 making no interactions with mRNA. Under that model, a U36C mutation would still induce -1 frameshifting, but experiments refute this. We perform all-atom simulations of wild-type tRNA(Ser3), as well as a U36C mutant. Our simulations revealed a hydrogen bond between U36 of the anticodon and G1 of the codon. The U36C mutant cannot make this interaction, as it lacks the hydrogen-bond-donating H3. The simulation thus suggests a novel, non-doublet decoding mechanism for -1 frameshifting by tRNA(Ser3) at Ala codons.