Dissecting macromolecular recognition sites in ribosome: implication to its self-assembly

Area of Science:

• Structural biology
• Molecular biology
• Biophysics

Background:

• Ribosome assembly is a complex process involving intricate macromolecular interactions.
• Previous studies on ribosomal interactions are limited to specific subunits or species.
• A comparative analysis across different domains of life is lacking.

Purpose of the Study:

• To comparatively analyze structural and physicochemical properties of protein-protein (PP), protein-RNA (PR), and RNA-RNA (RR) interfaces in ribosomal subunits.
• To develop a classifier for categorizing ribosomal proteins based on their binding properties.
• To gain insights into the dynamics of ribosome assembly and protein interactions.

Main Methods:

• Analysis of structural and physicochemical properties of PP, PR, and RR interfaces in prokaryotic and eukaryotic ribosomes.
• Development of a Random Forest (RF) classifier to predict ribosomal protein binding order.
• Comparative analysis of interface properties between small and large ribosomal subunits, and between subunits.

Main Results:

• Significant differences and similarities in macromolecular recognition sites were observed between prokaryotic and eukaryotic ribosomes.
• PR interfaces are larger and exhibit more ionic interactions than PP and RR interfaces.
• Eukaryotic interfaces are better packed than prokaryotic ones, but inter-subunit interfaces show low packing density.
• The RF classifier predicted r-protein assembly order with 80% accuracy.

Conclusions:

• Comparative analysis reveals conserved and divergent features of macromolecular interactions in ribosome assembly.
• Protein-RNA interactions play a critical role in ribosome assembly dynamics.
• The developed RF model offers a novel approach for classifying ribosomal proteins based on their assembly pathway.