Another look at mutations in ribosomal protein S4 lends strong support to the domain closure model

Abstract

Ribosomes employ a "kinetic discrimination" mechanism, in which correct substrates are incorporated more rapidly than incorrect ones. The structural basis of this mechanism may involve 30S domain closure, a global conformational change that coincides with codon recognition. In a direct screen for fidelity-altering mutations, Agarwal and coworkers (D. Agarwal, D. Kamath, S. T. Gregory, and M. O'Connor, J Bacteriol 197:1017-1025, 2015, doi:10.1128/JB.02485-14) isolated mutations that progressively truncate the C terminus of S4. All of these promote miscoding and undoubtedly destabilize the S4-S5 interface, consistent with the domain closure model.

FIG 1

A view of the S4-S5 region of the 30S subunit, with protein and RNA chains shown as simplified ribbon models. S4 is blue, except for the C-terminal portion, which is yellow. Amino acids corresponding to the positions of nonsense mutations isolated by Agarwal et al. are labeled (magenta; E. coli numbering). S5 is cyan. This image is based on Protein Data Bank entry 2J00.