Protein escape at the ribosomal exit tunnel: Effect of the tunnel shape

TL;DR

This study investigates how the shape of the ribosomal exit tunnel affects protein escape, showing that at physiological temperatures, escape times are rapid and comparable between atomistic and cylindrical models, with implications for ribosome function.

Contribution

It introduces an atomistic model of the ribosomal tunnel and compares protein escape dynamics to cylindrical models, revealing shape-dependent effects on trapping and escape times.

Findings

Escape times are sub-millisecond at physiological conditions.

Atomistic tunnel shape influences protein trapping at low temperatures.

All-$eta$ proteins escape faster than all-$\alpha$ proteins, but this difference diminishes with longer chains.

Abstract

We study the post-translational escape of nascent proteins at the ribosomal exit tunnel with the consideration of a real shape atomistic tunnel based on the Protein Data Bank (PDB) structure of the large ribosome subunit of archeon Haloarcula marismortui. Molecular dynamics simulations employing the Go-like model for the proteins show that at intermediate and high temperatures, including a presumable physiological temperature, the protein escape process at the atomistic tunnel is quantitatively similar to that at a cylinder tunnel of length L = 72 {\AA} and diameter d = 16 {\AA}. At low temperatures, the atomistic tunnel, however, yields an increased probability of protein trapping inside the tunnel while the cylinder tunnel does not cause the trapping. All-$\beta$ proteins tend to escape faster than all-$\alpha$ proteins but this difference is blurred on increasing the protein's chain length. A 29-residue zinc-finger domain is shown to be severely trapped inside the tunnel. Most of the single-domain proteins considered, however, can escape efficiently at the physiological temperature with the escape time distribution following the diffusion model proposed in our previous works. An extrapolation of the simulation data to a realistic value of the friction coefficient for amino acids indicates that the escape times of globular proteins are at the sub-millisecond scale. It is argued that this time scale is short enough for the smooth functioning of the ribosome by not allowing nascent proteins to jam the ribosome tunnel.