On the response of elongating ribosomes to forces opposing translocation.

The elongation phase of protein synthesis is a cyclic, steady-state process. It follows that its directionality is determined by the thermodynamics of the accompanying chemical reactions, which strongly favor elongation. Its irreversibility is guaranteed by its coupling to those reactions, rather being a consequence of any of the conformational changes that occur as it unfolds. It also follows that, in general, the rate of elongation is not proportional to the forward rate constants of any of its steps, including its final, mechano-chemical step, translocation. Instead, the reciprocal of the rate of elongation should be linearly related to the reciprocal of those rate constants. When the results of experiments done a decade ago to measure the effect that forces opposing translocation have on the rate of elongation are reinterpreted in light of these findings, it becomes clear that translocation was rate limiting under conditions in which those experiments were done, and that it is likely to be a Brownian ratchet process, as was concluded earlier.