James Nathan R, Brown Alan, Gordiyenko Yuliya, Ramakrishnan V
Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Science. 2016 Dec 16;354(6318):1437-1440. doi: 10.1126/science.aai9127. Epub 2016 Dec 1.
Ribosomes stall when they encounter the end of messenger RNA (mRNA) without an in-frame stop codon. In bacteria, these "nonstop" complexes can be rescued by alternative ribosome-rescue factor A (ArfA). We used electron cryomicroscopy to determine structures of ArfA bound to the ribosome with 3'-truncated mRNA, at resolutions ranging from 3.0 to 3.4 angstroms. ArfA binds within the ribosomal mRNA channel and substitutes for the absent stop codon in the A site by specifically recruiting release factor 2 (RF2), initially in a compact preaccommodated state. A similar conformation of RF2 may occur on stop codons, suggesting a general mechanism for release-factor-mediated translational termination in which a conformational switch leads to peptide release only when the appropriate signal is present in the A site.
当核糖体遇到没有框内终止密码子的信使核糖核酸(mRNA)末端时,就会发生停滞。在细菌中,这些“无义”复合物可被替代核糖体拯救因子A(ArfA)拯救。我们使用冷冻电子显微镜在3.0至3.4埃的分辨率下确定了ArfA与带有3'端截短mRNA的核糖体结合的结构。ArfA结合在核糖体mRNA通道内,并通过特异性招募释放因子2(RF2)来替代A位点中缺失的终止密码子,最初RF2处于紧密的预适应状态。RF2在终止密码子上可能会出现类似的构象,这表明释放因子介导的翻译终止存在一种普遍机制,即仅当A位点存在适当信号时,构象转换才会导致肽段释放。