在蛋白合成期间，核糖体在解码中心依照信使RNA (mRNA)上的三联体密码精确的选择转移RNA (tRNAs)。tRNA的选择开始于延伸因子Tu，它可以传递tRNA到氨酰tRNA结合位点即A位点，还可以在解码中心水解GTP来建立密码子-反密码子之间的相互作用。在随后的校对阶段，核糖体重新检查tRNA，如果被发现不能正确配对于A位点该tRNA便会被排除。过去一直认为，16S核糖体RNA普遍保守的G53、A1492和 A1493对tRNA结合在A位点至关重要，它们可以积极的监视同源性tRNA ，这种对正确配对的识别会引起核糖体整体构象的改变（即结构域闭合）。近日，法国斯特拉斯堡大学的Gulnara Yusupova等人研究发现了新的核糖体解码机制，相关研究发表在《自然》（Nature）上。
实验过程中，通过在校对阶段模拟同源的或者是近同源状态的编码中心，基于在3.1-3.4A分辨率下70S核糖体的六个X光结构，研究人员提出了一个完整的解码机制。研究表明：在结合同源的或者是近同源的tRNA时，30S亚基遭受了同样的结构域闭合。30S亚基的构象改变形成了一个解码中心，驱使mRNA A密码子的前两个核苷酸必须以Watson-Crick碱基配对方式严格配对。
当U·G和G·U错配时，一般被认为会形成不稳定的碱基对，在第一个或者是第二个密码子-反密码子位置，解码中心会迫使该配对通过几何变化接近于正确的C·G配对形式。这本身或者在密码子-反密码子的小螺旋及反密码子环存在扭曲，导致近同源的tRNA从核糖体离开。（生物谷Deepblue编译）
doi: 10.1038/nature10913
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A new understanding of the decoding principle on the ribosome
>Natalia Demeshkina, Lasse Jenner, Eric Westhof, Marat Yusupov & Gulnara Yusupoval.
During protein synthesis, the ribosome accurately selects transfer RNAs (tRNAs) in accordance with the messenger RNA (mRNA) triplet in the decoding centre. tRNA selection is initiated by elongation factor Tu, which delivers tRNA to the aminoacyl tRNA-binding site (A site) and hydrolyses GTP upon establishing codon–anticodon interactions in the decoding centre.At the following proofreading step the ribosome re-examines the tRNA and rejects it if it does not match the A codon. It was suggested that universally conserved G530, A1492 and A1493 of 16S ribosomal RNA, critical for tRNA binding in the A site, actively monitor cognate tRNA, and that recognition of the correct codon–anticodon duplex induces an overall ribosome conformational change (domain closure). Here we propose an integrated mechanism for decoding based on six X-ray structures of the 70S ribosome determined at 3.1–3.4A resolution, modelling cognate or near-cognate states of the decoding centre at the proofreading step. We show that the 30S subunit undergoes an identical domain closure upon binding of either cognate or near-cognate tRNA. This conformational change of the 30S subunit forms a decoding centre that constrains the mRNA in such a way that the first two nucleotides of the A codon are limited to form Watson–Crick base pairs.When U·G and G·U mismatches, generally considered to form wobble base pairs, are at the first or second codon–anticodon position, the decoding centre forces this pair to adopt the geometry close to that of a canonical C·G pair.This by itself, or with distortions in the codon–anticodon mini-helix and the anticodon loop, causes the near-cognate tRNA to dissociate from the ribosome.
