Portal de Periódicos da CAPES

Macrolide antibiotics allosterically predispose the ribosome for translation arrest

2014; National Academy of Sciences; Volume: 111; Issue: 27 Linguagem: Inglês

10.1073/pnas.1403586111

1091-6490

Shanmugapriya Sothiselvam, Bo Liu, Wei Han, Haripriya Ramu, Dorota Klepacki, Gemma C. Atkinson, Age Brauer, Maido Remm, Tanel Tenson, Klaus Schulten, Nora Vázquez‐Laslop, Alexander S. Mankin,

Peptidase Inhibition and Analysis

Significance Translation arrest regulated by nascent peptides and small cofactors controls expression of important genes, including medically relevant macrolide antibiotic resistance genes. The role of the cofactor for triggering this mechanism has remained enigmatic. Previous studies suggested that extensive interactions between the nascent chain and the antibiotic molecule juxtaposed in the ribosomal exit tunnel were critical for halting translation. However, here we show that the antibiotic induces stalling, even without significant contacts with the peptide, by allosterically altering the peptidyl transferase center. This finding unveils a previously unknown role of cofactors for translation arrest and demonstrates the existence of a functional link between the exit tunnel and the catalytic center of the ribosome.