The molecular architecture of protein-RNA interfaces are analyzed using a non-redundant dataset of 152 protein-RNA complexes. We find that an average protein-RNA interface is smaller than an average protein-DNA interface but larger than an average protein-protein interface. Among the different classes of protein-RNA complexes, interfaces with tRNA are the largest, while the interfaces with the single-stranded RNA are the smallest. Significantly, RNA contributes more to the interface area than its partner protein. Moreover, unlike protein-protein interfaces where the side chain contributes less to the interface area compared to the main chain, the main chain and side chain contributions flipped in protein-RNA interfaces. We find that the protein surface in contact with the RNA in protein-RNA complexes is better packed than that in contact with the DNA in protein-DNA complexes, but loosely packed than that in contact with the protein in protein-protein complexes. Shape complementarity and electrostatic potential are the two major factors that determine the specificity of the protein-RNA interaction. We find that the H-bond density at the protein-RNA interfaces is similar with that of protein-DNA interfaces but higher than the protein-protein interfaces. Unlike protein-DNA interfaces where the deoxyribose has little role in intermolecular H-bonds, due to the presence of an oxygen atom at the 2' position, the ribose in RNA plays significant role in protein-RNA H-bonds. We find that besides H-bonds, salt bridges and stacking interactions also play significant role in stabilizing protein-nucleic acids interfaces; however, their contribution at the protein-protein interfaces is insignificant.
Interactions between macromolecules play a crucial role in ribosome assembly that follows a highly coordinated process involving RNA folding and binding of ribosomal proteins (r-proteins). Although extensive studies have been carried out to understand macromolecular interactions in ribosomes, most of them are confined to either large or small ribosomal-subunit of few species. A comparative analysis of macromolecular interactions across different domains is still missing. We have analyzed the structural and physicochemical properties of protein-protein (PP), protein-RNA (PR) and RNA-RNA (RR) interfaces in small and large subunits of ribosomes, as well as in between the two subunits. Additionally, we have also developed Random Forest (RF) classifier to catalog the r-proteins. We find significant differences as well as similarities in macromolecular recognition sites between ribosomal assemblies of prokaryotes and eukaryotes. PR interfaces are substantially larger and have more ionic interactions than PP and RR interfaces in both prokaryotes and eukaryotes. PP, PR and RR interfaces in eukaryotes are well packed compared to those in prokaryotes. However, the packing density between the large and the small subunit interfaces in the entire assembly is strikingly low in both prokaryotes and eukaryotes, indicating the periodic association and dissociation of the two subunits during the translation. The structural and physicochemical properties of PR interfaces are used to predict the r-proteins in the assembly pathway into early, intermediate and late binders using RF classifier with an accuracy of 80%. The results provide new insights into the classification of r-proteins in the assembly pathway.
The 26S proteasome is a multi-catalytic ATP-dependent protease complex that recognizes and cleaves damaged or misfolded proteins to maintain cellular homeostasis.The 26S subunit consists of 20S core and 19S regulatory particles. 20S core particle consists of a stack of heptameric alpha and beta subunits. To elucidate the structurefunction relationship, we have dissected protein-protein interfaces of 20S core particle and analyzed structural and physiochemical properties of intra-alpha, intra-beta, inter-beta, and alpha-beta interfaces. Furthermore, we have studied the evolutionary conservation of 20S core particle. We find the size of intra-alpha interfaces is significantly larger and is more hydrophobic compared with other interfaces. Inter-beta interfaces are well packed, more polar, and have higher salt-bridge density than other interfaces. In proteasome assembly, residues in beta subunits are better conserved than alpha subunits, while multi-interface residues are the most conserved. Among all the residues at the interfaces of both alpha and beta subunits, Gly is highly conserved. The largest size of intra-alpha interfaces complies with the hypothesis that large interfaces form first during the 20S assembly. The tight packing of inter-beta interfaces makes the core particle impenetrable from outer wall of the cylinder. Comparing the three domains, eukaryotes have large and well-packed interfaces followed by archaea and bacteria. Our findings provide a structural basis of assembly of 20S core particle in all the three domains of life. KEYWORDS20S core particle, evolutionary conservation, interaction network, proteasome assembly, proteinprotein interfaces
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