A model for the role of isomerization in nascent peptide movement through the ribosomal tunnel

The ribosome is a molecular machine whose manner of controlling the progression of the nascent chain through the ribosomal exit tunnel is currently unknown. A novel model for the mechanism driving the nascent chain motion is hereby presented, in which the similar to 180 degrees rotatory motion performed by each C-terminal amino acid of the nascent chain during its translocation from the A site to the P site, is suggested to twist the newly formed peptide bond into cis conformation. By catalyzing the cis to trans isomerization, the ribosome is proposed to release the potential energy stored within the cis conformer and to utilize it to push the chain down the tunnel, thus operating as a molecular motor. This hypothetical isomerization mechanism is supported by its ability to provide an explanation for the peculiar conduct observed in translational events of nascent chains with C-terminal prolines: the slow peptide bond formation with puromycin, translation arrest, and tmRNA tagging.-Agmon, I. C. A model for the role of isomerization in nascent peptide movement through the ribosomal tunnel. FASEB J. 26, 2277-2282 (2012). www.fasebj.org