Biology subjects

Kushner, A.

Publications and source records attributed to Kushner, A..

3 recordsLinked to original sources

bioRxiv2025

Advanced coarse-grained model for fast simulation of nascent polypeptide chain dynamics within the ribosome

The nascent polypeptide exit tunnel (NPET) is a sub-compartment of the ribosome that constrains the dynamics of nascent polypeptide chains during protein translation. Simulating these dynamics has been limited due by the spatial scale of the ribosome and the temporal scale of elongation. Here, we present an automated pipeline to extract the geometry of the NPET and the ribosome surface at high resolution from any ribosome structure. We further convert this into a coarse-grained (CG) bead model that can be used in molecular simulations. This CG model more accurately captures NPET geometry than previous representations and allows for the simulation of co- and post-translational processes that are computationally prohibitive with all-atom approaches. In particular, we illustrate how the CG model may be used to simulate the elongation dynamics of the nascent polypeptide and its escape post-translation, as well as evaluate free energy landscapes and examine the influence of electrostatics on the nascent polypeptide escape. SIGNIFICANCEThe translation of nascent polypeptide chains is mediated by the ribosome, with interactions between the protein and the nascent polypeptide exit tunnel (NPET) impacting the process. However, modeling and simulating protein elongation and its escape from the NPET remain challenging due to computational limitations in spatial and temporal resolution. Here, we develop a computational pipeline for generating coarse-grained (CG) models of the NPET and ribosome surface from any ribosome structure that allow for both effective and accurate computer simulations. We demonstrate how the model can be implemented for various simulations, including the elongation dynamics of the nascent polypeptide and escape of the chain post-translation, as well as in estimating free energy landscapes and examining the impact of the charged environment on the escape time.

biophysics↗

bioRxiv2025

Detection of archaeal- and prokaryotic-like ribosome exit tunnels within eukaryotic kingdoms

The ribosome exit tunnel is a critical sub-compartment that actively regulates the folding and dynamics of nascent polypeptide chains during protein translation. In this study, we systematically examined tunnel structures of 725 ribosome models obtained through cryo-EM and X-ray crystallography, to quantify structural variations across different species and biological domains. Hierarchical clustering revealed significant geometric differences between prokaryotic and eukaryotic ribosomes, with a surprising discovery: six eukaryotic protist species display tunnel structures remarkably similar to those of archaea and bacteria. By analyzing the sequences and structures of ribosomal components forming the tunnel walls, we identified four specific sequence modifications in ribosomal proteins and ribosomal RNAs (rRNA) responsible for these unique geometric variations, and detected these modifications in additional protist species lacking existing 3D structural data. Overall, our findings highlights some complex evolutionary mechanisms governing ribosomal protein and large subunit rRNA, providing novel insights into the tunnels regulatory role in protein translation.

molecular biology↗

bioRxiv2022

RiboXYZ: A comprehensive database for visualizing and analyzing ribosomestructures

Recent advances in Cryo-EM led to a surge of ribosome structures deposited over the past years, including structures from different species, conformational states, or bound with different ligands. Yet, multiple conflicts of nomenclature make the identification and comparison of structures and ortholog components challenging. We present RiboXYZ (available at https://ribosome.xyz), a database that provides organized access to ribosome structures, with several tools for visualisation and study. The database is up-to-date with the Protein Data Bank (PDB) but provides a standardized nomenclature that allows for searching and comparing ribosomal components (proteins, RNA, ligands) across all the available structures. In addition to structured and simplified access to the data, the application has several specialized visualization tools, including the identification and prediction of ligand binding sites, and 3D superimposition of ribosomal components. Overall, RiboXYZ provides a useful toolkit that complements the PDB database, by implementing the current conventions and providing a set of auxiliary tools that have been developed explicitly for analyzing ribosome structures. This toolkit can be easily accessible by both experts and non-experts in structural biology so that they can search, visualize and compare structures, with various potential applications in molecular biology, evolution, and biochemistry.

molecular biology↗