Peptides in the Ribosomal Tunnel Talk Back Daniel N. Wilson  Molecular Cell  Volume 41, Issue 3, Pages 247-248 (February 2011) DOI: 10.1016/j.molcel.2011.01.017 Copyright © 2011 Elsevier Inc. Terms and Conditions

Figure 1 Mechanistic Insights into ErmCL- and ErmAL-Mediated Translational Arrest (A) In the absence of erythromycin, stem combinations 1 + 2 and 3 + 4 are favored, leading to repression of ermC due to the sequestering of the ribosome-binding site (RBS) and AUG start codon of ermC within the 3 + 4 stem loop. In the presence of subinhibitory concentrations of erythromycin, stalling of the ribosome at the ninth codon (Ile9) during translation of ermCL leads to an alternative 2 + 3 stem loop, allowing ribosomes to access the RBS and AUG of the ermC gene. In contrast, translational stalling of ErmAL1 occurs when the eighth codon (Val8) is in the P-site. (B) Schematic of the ErmCL stalling ribosome, with ErmCL-tRNAIle in the P-site (gold) and the tenth codon encoding Ser-tRNASer located in the A-site. Interaction between erythromycin (blue), the ErmCL peptide, and the ribosome relays a signal (arrowed) back to inactivate the peptidyl transferase center (PTC). (C) In the presence of erythromycin (Ery) and ErmAL1 (Ala is −2 position), the A-site of the peptidyl transferase center (PTC) becomes selective: Peptide bond formation with certain amino acids is abolished (red) or becomes very slow (orange), leading to stalling or partial stalling, but other amino acids are permitted (green), and no stalling ensues. (D) In contrast, ErmCL (Phe at −2 position) renders the A-site restrictive, preventing all amino acids from forming peptide bonds, leading to translational stalling. (E) Two possible signal-relay pathways (arrowed) communicating the information from the ribosomal exit tunnel to the PTC A-site. Erythromycin, blue; ErmAL-tRNA in the P-site (yellow) has the −2 position colored red. The aminoacyl moiety of the A-site tRNA (gray) inserts into the cleft between A2451 and A2452 (light blue) of the 23S rRNA. Other potential nucleotides involved in the relays include A2503 and U2504 (cyan) as well as A2062 and G2061 (teal). Molecular Cell 2011 41, 247-248DOI: (10.1016/j.molcel.2011.01.017) Copyright © 2011 Elsevier Inc. Terms and Conditions