Department of Cell and Molecular Biology, Uppsala University, Uppsala 75124, Sweden; email:
Annu Rev Biophys. 2018 May 20;47:525-548. doi: 10.1146/annurev-biophys-060414-034148.
Accurate translation of genetic information is crucial for synthesis of functional proteins in all organisms. We use recent experimental data to discuss how induced fit affects accuracy of initial codon selection on the ribosome by aminoacyl transfer RNA in ternary complex ( T) with elongation factor Tu (EF-Tu) and guanosine-5'-triphosphate (GTP). We define actual accuracy ([Formula: see text]) of a particular protein synthesis system as its current accuracy and the effective selectivity ([Formula: see text]) as [Formula: see text] in the limit of zero ribosomal binding affinity for T. Intrinsic selectivity ([Formula: see text]), defined as the upper thermodynamic limit of [Formula: see text], is determined by the free energy difference between near-cognate and cognate T in the pre-GTP hydrolysis state on the ribosome. [Formula: see text] is much larger than [Formula: see text], suggesting the possibility of a considerable increase in [Formula: see text] and [Formula: see text] at negligible kinetic cost. Induced fit increases [Formula: see text] and [Formula: see text] without affecting [Formula: see text], and aminoglycoside antibiotics reduce [Formula: see text] and [Formula: see text] at unaltered [Formula: see text].
准确翻译遗传信息对于所有生物体中功能性蛋白质的合成至关重要。我们利用最新的实验数据来讨论诱导契合如何影响氨酰基转移 RNA 在延伸因子 Tu（EF-Tu）和鸟苷 5'-三磷酸（GTP）存在的三元复合物（T）与核糖体结合时初始密码子选择的准确性。我们将特定蛋白质合成系统的实际准确性([Formula: see text])定义为其当前准确性，将有效选择性([Formula: see text])定义为零核糖体对 T 的结合亲和力时的[Formula: see text]。内在选择性([Formula: see text])定义为核糖体上 GTP 水解前近同功和同功 T 之间的自由能差的热力学上限，由近同功和同功 T 之间的自由能差决定。[Formula: see text]远大于[Formula: see text]，这表明在几乎没有动力学成本的情况下，[Formula: see text]和[Formula: see text]可能会有相当大的提高。诱导契合增加了[Formula: see text]和[Formula: see text]，而不影响[Formula: see text]，氨基糖苷类抗生素降低了[Formula: see text]和[Formula: see text]，而[Formula: see text]不变。
