Drug Sensing by the Ribosome Induces Translational Arrest via Active Site Perturbation

作者：Arenz Stefan; Meydan Sezen; Starosta Agata L; Berninghausen Otto; Beckmann Roland; Vazquez Laslop Nora; Wilson Daniel N^*

来源：Molecular Cell, 2014, 56(3): 446-452.

DOI：10.1016/j.molcel.2014.09.014

During protein synthesis, nascent polypeptide chains within the ribosomal tunnel can act in cis to induce ribosome stalling and regulate expression of downstream genes. The Staphylococcus aureus ErmCL leader peptide induces stalling in the presence of clinically important macrolide antibiotics, such as erythromycin, leading to the induction of the downstream macrolide resistance methyltransferase ErmC. Here, we present a cryo-electron microscopy (EM) structure of the erythromycindependent ErmCL-stalled ribosome at 3.9 angstrom resolution. The structure reveals how the ErmCL nascent chain directly senses the presence of the tunnel-bound drug and thereby induces allosteric conformational rearrangements at the peptidyltransferase center (PTC) of the ribosome. ErmCL-induced perturbations of the PTC prevent stable binding and accommodation of the aminoacyl-tRNA at the A-site, leading to inhibition of peptide bond formation and translation arrest.

• 出版日期2014-11-6