Svidritskiy Egor, Korostelev Andrei A
RNA Therapeutics Institute, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
RNA Therapeutics Institute, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Structure. 2015 Nov 3;23(11):2155-61. doi: 10.1016/j.str.2015.08.011. Epub 2015 Sep 24.
Translation initiation in the P site occasionally occurs at atypical (non-AUG) start codons, including those forming a mismatch in the third (wobble) position. During elongation, however, a pyrimidine-pyrimidine wobble mismatch may trigger a translation quality-control mechanism, whereby the P-site mismatch is thought to perturb the downstream A-site codon or the decoding center, thereby reducing translation fidelity and inducing termination of aberrant translation. We report a crystal structure of the 70S initiation complex containing an AUC codon in the ribosomal P site. Remarkably, the ribosome stabilizes the mismatched codon-anticodon helix, arranging a normally disruptive cytosine-cytosine pair into a Watson-Crick-like conformation. Translation-competent conformations of the tRNA, mRNA, and decoding center suggest that a P-site wobble-position mismatch in the 70S initiation complex does not pre-arrange the mRNA or decoding center to favor subsequent miscoding events.
在P位点的翻译起始偶尔会发生在非典型（非AUG）起始密码子处，包括那些在第三位（摆动）位置形成错配的密码子。然而，在延伸过程中，嘧啶-嘧啶摆动错配可能会触发翻译质量控制机制，据此认为P位点错配会扰乱下游A位点密码子或解码中心，从而降低翻译保真度并诱导异常翻译的终止。我们报道了一种核糖体P位点含有AUC密码子的70S起始复合物的晶体结构。值得注意的是，核糖体稳定了错配的密码子-反密码子螺旋，将通常具有干扰性的胞嘧啶-胞嘧啶对排列成类似沃森-克里克的构象。tRNA、mRNA和解码中心的具有翻译活性的构象表明，70S起始复合物中P位点摆动位置的错配不会预先安排mRNA或解码中心以利于随后的错义编码事件。
