Abstract
BackgroundThe maintenance of protein structural stability requires the cooperativity among spatially neighboring residues. Previous studies have shown that conserved residues tend to occur clustered together within enzyme active sites and protein-protein/DNA interfaces. It is possible that conserved residues form one or more local clusters in protein tertiary structures as it can facilitate the formation of functional motifs. In this work, we systematically investigate the spatial distributions of conserved residues as well as hot spot ones within protein-RNA interfaces.ResultsThe analysis of 191 polypeptide chains from 160 complexes shows the polypeptides interacting with tRNAs evolve relatively rapidly. A statistical analysis of residues in different regions shows that the interface residues are often more conserved, while the most conserved ones are those occurring at protein interiors which maintain the stability of folded polypeptide chains. Additionally, we found that 77.8% of the interfaces have the conserved residues clustered within the entire interface regions. Appling the clustering characteristics to the identification of the real interface, there are 31.1% of cases where the real interfaces are ranked in top 10% of 1000 randomly generated surface patches. In the conserved clusters, the preferred residues are the hydrophobic (Leu, Ile, Met), aromatic (Tyr, Phe, Trp) and interestingly only one positively charged Arg residues. For the hot spot residues, 51.5% of them are situated in the conserved residue clusters, and they are largely consistent with the preferred residue types in the conserved clusters.ConclusionsThe protein-RNA interface residues are often more conserved than non-interface surface ones. The conserved interface residues occur more spatially clustered relative to the entire interface residues. The high consistence of hot spot residue types and the preferred residue types in the conserved clusters has important implications for the experimental alanine scanning mutagenesis study. This work deepens the understanding of the residual organization at protein-RNA interface and is of potential applications in the identification of binding site and hot spot residues.
Highlights
Protein-RNA interactions play important roles in a wide variety of cellular processes, such as regulation of gene expression, RNA splicing, protein synthesis and virus assembly [1, 2]
College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China interfaces experience relatively higher evolutionary pressures, and interface residues are generally more conserved [4, 5]. How are these conserved residues organized at protein-RNA interfaces? Are they scattered across the interface, or clustered together in three dimensions? How are the preferences of residue types and hot spot residues for different interface regions? Whether can these characteristics be used to identify the real interface? These questions are not quite clear currently
Ahmad et al found that for the proteins interacting with DNAs, about half of the observed conserved residue clusters are in the interfaces with DNAs and the remaining are in the interfaces with proteins or ligands, or embedded in the structural scaffolds [7]
Summary
Protein-RNA interactions play important roles in a wide variety of cellular processes, such as regulation of gene expression, RNA splicing, protein synthesis and virus assembly [1, 2]. It is likely that the most stabilizing residues or putative hot spot residues are those that occur as clusters of conserved residues, contributing more to the stability and function of interactions than others, which has been confirmed in protein-DNA interfaces by Ahmad et al [7]. Landgraf et al and Madabushi’s group have found that in protein tertiary structures and enzyme active sites, the evolutionary conserved residues occur clustered together [8, 9]. These conserved residues form one or more localized clusters within the tertiary structure or interface, which will facilitate the formation of “functional motifs”. Previous studies have shown that conserved residues tend to occur clustered together within enzyme active sites and protein-protein/DNA interfaces. We systematically investigate the spatial distributions of conserved residues as well as hot spot ones within protein-RNA interfaces
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