Figure 2. Macrolides arrest the ribosome at specific mRNA codons.

(A) Treatment of E. coli cells with high concentrations of ERY or TEL leads to dramatic redistribution of ribosomes along the genes (illustrated by the ribosome densities in the representative gene argS). The discrete peaks of ribosome density at specific codons of argS in the ERY- or TEL-treated cells reflect context-specific translation arrest [24, 25].

(B) Some ORFs are completely translated in macrolide-treated cells. The occurrence of ribosome density throughout the representative gene hns in cells treated with TEL reveals HN-S as one of the proteins fully translated in the presence of this antibiotic (See Figure 1D).

(C) Ribosome with bound macrolide struggles to polymerize specific sequences, the Macrolide Problematic Motifs (MAMs). The table lists the 10 most prevalent MAMs enriched in the sites of translation arrest in the TEL- and ERY-treated cells [25]. The consensus sequences of the common MAMs are listed underneath the table (‘X’ indicates any amino acid, ‘+’ indicates Arg or Lys).

(D) Translation arrest at an MAM can be influenced by a more extended context, likely involving other segments of the nascent protein chain. The shown example illustrates how TEL-bound ribosomes could easily translate through the usually problematic Arg-Glu-Lys sequence (an MAM of the + X + type) present within the early codons of rpmC but became arrested at the second +X+ MAM (Arg-Val-Lys) located towards the end of the ORF.