Chan Yuen-Ling, Wool Ira G
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
J Mol Biol. 2008 Apr 18;378(1):12-9. doi: 10.1016/j.jmb.2008.02.016. Epub 2008 Feb 15.
The elongation stage of protein synthesis consists of repeated cycles of the binding of aminoacyl-tRNA, peptide bond formation, and translocation. The process is normally catalyzed by the elongation factors Tu and G; however, the reactions can proceed, at least in prescribed and limited circumstance, in the absence of the elongation factors, a finding that strongly implies that the chemistry of protein synthesis is inherent in the ribosome. The sarcin/ricin domain in 23 S rRNA, the site of inactivation of ribosomes by ribotoxins, is where the elongation factors bind. The question that arises is whether the sarcin/ricin domain is necessary for factor-independent peptide synthesis. The answer is that it is not. The disruption of the sarcin/ricin domain by covalent modification with either sarcin or pokeweed antiviral protein did not affect factor-independent peptide synthesis; nor did lethal mutations of nucleotides that abolish the binding of elongation factors. The results imply that the sole function of the sarcin/ricin domain is to provide a binding site for the elongation factors and, hence, to facilitate the elongation reactions. The results also raise the possibility of the co-evolution of the sarcin/ricin domain and the elongation factors.
蛋白质合成的延伸阶段由氨酰 - tRNA结合、肽键形成和转位的重复循环组成。该过程通常由延伸因子Tu和G催化；然而，至少在特定且有限的情况下，反应可以在没有延伸因子的情况下进行，这一发现强烈表明蛋白质合成的化学过程是核糖体固有的。23S rRNA中的帚曲霉素/蓖麻毒素结构域是核糖体毒素使核糖体失活的位点，也是延伸因子结合的地方。由此产生的问题是，帚曲霉素/蓖麻毒素结构域对于不依赖因子的肽合成是否必要。答案是否定的。用帚曲霉素或商陆抗病毒蛋白进行共价修饰破坏帚曲霉素/蓖麻毒素结构域，并不影响不依赖因子的肽合成；消除延伸因子结合的核苷酸致死突变也不影响。结果表明，帚曲霉素/蓖麻毒素结构域的唯一功能是为延伸因子提供一个结合位点，从而促进延伸反应。结果还提出了帚曲霉素/蓖麻毒素结构域和延伸因子共同进化的可能性。
