Grisé-Miron L, Noreau J, Melançon P, Brakier-Gingras L
Biochim Biophys Acta. 1981 Nov 27;656(1):103-10. doi: 10.1016/0005-2787(81)90032-0.
In a poly(U)-programmed translation system, neomycin stimulates the misincorporation of tyrosine and of serine which, according to Thompson and Stone (Thompson, R.C. and Stone, P.J. (1977) Proc. Natl. Acad. Sci. USA. 74, 198-202), are normally rejected at an initial discrimination step during the binding of charged tRNAs to the ribosome. In contrast, streptomycin favors the misincorporation of isoleucine which is normally rejected at a subsequent GTP-dependent discrimination step, the so-called proofreading step. The labeling of the ribosome with N-ethylmaleimide mimics the effect of streptomycin in that it stimulates the misincorporation of isoleucine but not of tyrosine or serine. This effect is correlated with the labeling of protein S18 but not with that of protein S1. These observations indicate that the sulfhydryl group of protein S18 is located within a ribosomal domain involved in the proofreading control of tRNA selection. Taking into account our previous results that streptomycin and neomycin perturb ribosomal areas around the sulfhydryl groups of proteins S18 and S1, respectively, we suggest that these antibiotics induce misreading by different mechanisms which are linked to such perturbations.
在一个以聚尿苷酸（poly(U)）编程的翻译系统中，新霉素会刺激酪氨酸和丝氨酸的错误掺入。根据汤普森和斯通（汤普森，R.C. 以及斯通，P.J.（1977年）《美国国家科学院院刊》。74，198 - 202）的研究，在带电荷的转运RNA（tRNA）与核糖体结合的初始识别步骤中，这些氨基酸通常会被拒绝掺入。相比之下，链霉素有利于异亮氨酸的错误掺入，而异亮氨酸通常会在随后的依赖鸟苷三磷酸（GTP）的识别步骤，即所谓的校对步骤中被拒绝掺入。用N - 乙基马来酰亚胺标记核糖体模拟了链霉素的作用，因为它刺激了异亮氨酸的错误掺入，但不影响酪氨酸或丝氨酸的错误掺入。这种效应与蛋白质S18的标记相关，而与蛋白质S1的标记无关。这些观察结果表明，蛋白质S18的巯基位于核糖体中参与tRNA选择校对控制的结构域内。考虑到我们之前的结果，即链霉素和新霉素分别干扰了蛋白质S18和S1巯基周围的核糖体区域，我们认为这些抗生素通过与这种干扰相关的不同机制诱导错读。
