Distribution of dwell times of a ribosome: effects of infidelity, kinetic proofreading and ribosome crowding

TL;DR

This paper presents a theoretical model for the dwell time distribution of ribosomes during protein synthesis, incorporating effects of infidelity, kinetic proofreading, and crowding, with predictions aligning with existing data.

Contribution

The model captures key steps of the ribosome's mechano-chemical cycle and provides analytical expressions for dwell time distributions, including effects of quality control and crowding.

Findings

Analytical expression for dwell time distribution derived.

Model predictions consistent with experimental data.

Proposed experiments to test effects of ribosome quality control and crowding.

Abstract

Ribosome is a molecular machine that polymerizes a protein where the sequence of the amino acid residues, the monomers of the protein, is dictated by the sequence of codons (triplets of nucleotides) on a messenger RNA (mRNA) that serves as the template. The ribosome is a molecular motor that utilizes the template mRNA strand also as the track. Thus, in each step the ribosome moves forward by one codon and, simultaneously, elongates the protein by one amino acid. We present a theoretical model that captures most of the main steps in the mechano-chemical cycle of a ribosome. The stochastic movement of the ribosome consists of an alternating sequence of pause and translocation; the sum of the durations of a pause and the following translocation is the time of dwell of the ribosome at the corresponding codon. We derive the analytical expression for the distribution of the dwell times of a ribosome in our model. Whereever experimental data are available, our theoretical predictions are consistent with those results. We suggest appropriate experiments to test the new predictions of our model, particularly, the effects of the quality control mechanism of the ribosome and that of their crowding on the mRNA track.