Substrate-Induced Formation of Ribosomal Decoding Center for Accurate and Rapid Genetic Code Translation.

ABSTRACT

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 ( T3) 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 T3. 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 T3 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].