Terminating eukaryote translation: Domain 1 of release factor eRF1 functions in stop codon recognition
Terminating eukaryote translation: Domain 1 of release factor eRF1 functions in stop codon recognition
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DOI：
10.1017/s1355838200000777
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发表时间：
2000-09-01
期刊：
影响因子：
4.5
通讯作者：
Stansfield, I
中科院分区：
文献类型：
--
作者：
Bertram, G;Bell, HA;Stansfield, I
当释放因子eRF 1与eRF 3形成复合物，与三个终止密码子之一结合时，真核生物核糖体翻译终止。eRF 1的三级结构和大小与tRNA相似，支持释放因子可能作为tRNA的分子模拟物的假设。（类似于tRNA反密码子），进行遗传筛选以选择仅对三个终止密码子中的一个失能识别的突变体，10个分离的突变中有9个映射到eRF 1 N-末端结构域1内的保守残基。这些突变体的一个子集，尽管对于核糖体和eRF 3相互作用是野生型的，但它们各自识别三个终止密码子中的每一个的能力不同，这些终止密码子特异性突变体中的六个中的五个限定了酵母结构域1残基（I32、M48、V68、L123和H129），其位于eRF 1结构域1分子表面上的三个口袋中，终止密码子可以被模拟到所述口袋中。因此，遗传筛选结果和突变体表型与结构域1在终止密码子识别中的作用一致;该eRF 1结构域的拓扑结构以及eRF 1-终止密码子复合物建模进一步支持该结构域可能代表终止密码子结合位点本身的提议。
Eukaryote ribosomal translation is terminated when release factor eRF1, in a complex with eRF3, binds to one of the three stop codons. The tertiary structure and dimensions of eRF1 are similar to that of a tRNA, supporting the hypothesis that release factors may act as molecular mimics of tRNAs, To identify the yeast eRF1 stop codon recognition domain (analogous to a tRNA anticodon), a genetic screen was performed to select for mutants with disabled recognition of only one of the three stop codons, Nine out of ten mutations isolated map to conserved residues within the eRF1 N-terminal domain 1.A subset of these mutants, although wild-type for ribosome and eRF3 interaction, differ in their respective abilities to recognize each of the three stop codons, indicating codon-specific discrimination defects, Five of six of these stop codon-specific mutants define yeast domain 1 residues (I32, M48, V68, L123, and H129) that locate at three pockets on the eRF1 domain 1 molecular surface into which a stop codon can be modeled. The genetic screen results and the mutant phenotypes are therefore consistent with a role for domain 1 in stop codon recognition; the topology of this eRF1 domain, together with eRF1-stop codon complex modeling further supports the proposal that this domain may represent the site of stop codon binding itself.