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Modeling Ribosomal Translocation Facilitated by Peptidyl Transferase Antibiotics

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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.

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Notes

  1. As discussed in detail before,55 available structural data showed that the ribosomes complexed with tRNAs in the classical non-rotated state always have no or nearly no 30S head rotation5,11,15,22–25,40,44,58. It is thus expected that during the translocation the ribosomal complex with no intersubunit rotation has the non-rotated 30S head, implying that the forward 30S head rotation can only take place in the rotated/hybrid state. Based on these structural data, it is also proposed that the transition from the rotated/hybrid state to the non-rotated state is accompanied or followed immediately by the reverse rotation of the 30S head if it is rotated. As shown before,55 with this proposal the theoretical data are in good agreement with the biochemical data.19

  2. Biochemical data indicated that without a tRNA anticodon stem-loop bound to the 30S A site the translocation is inefficient even in the presence of EF-G.GTP, and only with a tRNA anticodon stem-loop bound to the 30S A site can the EF-G-catalyzed translocation become highly efficient.23 This could imply that the EF-G-catalyzed forward rotation of the 30S head is also mainly via the interaction of EF-G with the tRNA anticodon stem-loop bound to the 30S A site.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 11374352).

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Ping Xie declares that he has no conflicts of interest.

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  1. Key Laboratory of Soft Matter Physics and Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, 100190, China

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Associate Editor James L. McGrath oversaw the review of this article.

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Xie, P. Modeling Ribosomal Translocation Facilitated by Peptidyl Transferase Antibiotics. Cel. Mol. Bioeng. 9, 289–302 (2016). https://doi.org/10.1007/s12195-016-0433-z

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