Effect of Nascent Peptide Steric Bulk on Elongation Kinetics in the Ribosome Exit Tunnel

- A systematic increase of side-chain size induces rank-order slowing of elongation rate in upper, but not lower, tunnel regions.
- Increased side-chain volume leads to increased van der Waals interactions between nascent peptide and ribosome tunnel.
- A two-step translation strategy was developed to evaluate the effects of bulky side chains on elongation kinetics.

All proteins are synthesized by the ribosome, a macromolecular complex that accomplishes the life-sustaining tasks of faithfully decoding mRNA and catalyzing peptide bond formation at the peptidyl transferase center (PTC). The ribosome has evolved an exit tunnel to host the elongating new peptide, protect it from proteolytic digestion, and guide its emergence. It is here that the nascent chain begins to fold. This folding process depends on the rate of translation at the PTC. We report here that besides PTC events, translation kinetics depend on steric constraints on nascent peptide side chains and that confined movements of cramped side chains within and through the tunnel fine-tune elongation rates.

Graphical Abstract148