Molecular mechanism of stop codon recognition by eRF1

ETF1/eRF1，最近被认为是一种髓系肿瘤抑制基因，编码i类释放因子，在基因表达的翻译终止过程中识别帧内停止密码子。该蛋白因子eRF1（真核释放因子1）识别所有三个终止密码子，UAA， UGA和UAG，但不识别Trp密码子UGG。这种区分必须在eRF1的识别域中进行一些构象改变，因为如果eRF1仅仅通过将A/G结合为第二个字母，A/G结合为第三个字母来识别停止密码子，则无法消除UGG密码子。为了研究停止密码子识别的机制，我们制备了^<15>N标记和^<15>N/^<13> c标记的密码子识别结构域，分配了天然非脯氨酸脊骨残基的所有^1H^N和^<15>N共振，并利用核磁共振光谱分析了该结构域的动态结构。

ETF1/eRF1,which has recently been suggested to be a myeloid tumor suppressor gene, codes for the class-I release factor which recognizes an in-frame stop codon in translation termination processes of gene expression. This proteinaceous factor eRF1(eukaryotic release factor 1) recognizes all of the three stop codons, UAA, UGA and UAG, but not the Trp codon UGG. This discrimination must require some conformational changes in the recognition domain of eRF1,because the UGG codon cannot be eliminated if eRF1 recognizes the stop codons by simply binding to A/G as the 2nd letter and A/G the 3rd. To address the mechanism of stop codon recognition, we prepared ^<15>N-labeled and ^<15>N/^<13>C-labeled codon recognition domains, assigned all ^1H^N and ^<15>N resonances of native non-proline back bone residues, and now are analyzing dynamic structure of this domain by NMR spectroscopy.