Modeling Ribosomal Translocation Facilitated by Peptidyl Transferase Antibiotics

Abstract

The peptidyl transferase antibiotic sparsomycin can induce efficient ribosomal translocation in the absence of EF-G and GTP. However, how the antibiotic facilitates the translocation is unclear. Here, two models of antibiotic-induced translocation are considered, in which the interaction of the antibiotic with the peptidyl-tRNA in the A/P state, besides behaving as a pawl in the “Brownian ratchet”, also has an effect of compromising the interaction of the 30S subunit with the mRNA-tRNA complex (Model I) or facilitating the forward 30S head rotation which results in the ribosomal unlocking (Model II). It is shown that although the results obtained with Model I can explain the available experimental data on the translocation through the single-stranded mRNA, they are inconsistent with the experimental data on the translocation through the mRNA duplex; by contrast, the results obtained with Model II can explain quantitatively all of the available experimental data. With model II it is further shown that the efficient translocation induced by the binding of sparsomycin results mainly from the facilitation of the forward 30S head rotation, whereas the effect as the pawl plays only a little role. In addition, it is noted that the mRNA movement is brought about by the reverse intersubunit rotation rather than driven directly by the forward 30S head rotation, and the mechanism of antibiotic-induced translocation is similar to that of EF-G-catalyzed translocation.