Local Structural Differences in Homologous Proteins: Specificities in Different SCOP Classes

Abstract

The constant increase in the number of solved protein structures is of great help in understanding the basic principles behind protein folding and evolution. 3-D structural knowledge is valuable in designing and developing methods for comparison, modelling and prediction of protein structures. These approaches for structure analysis can be directly implicated in studying protein function and for drug design. The backbone of a protein structure favours certain local conformations which include α-helices, β-strands and turns. Libraries of limited number of local conformations (Structural Alphabets) were developed in the past to obtain a useful categorization of backbone conformation. Protein Block (PB) is one such Structural Alphabet that gave a reasonable structure approximation of 0.42 Å. In this study, we use PB description of local structures to analyse conformations that are preferred sites for structural variations and insertions, among group of related folds. This knowledge can be utilized in improving tools for structure comparison that work by analysing local structure similarities. Conformational differences between homologous proteins are known to occur often in the regions comprising turns and loops. Interestingly, these differences are found to have specific preferences depending upon the structural classes of proteins. Such class-specific preferences are mainly seen in the all-β class with changes involving short helical conformations and hairpin turns. A test carried out on a benchmark dataset also indicates that the use of knowledge on the class specific variations can improve the performance of a PB based structure comparison approach. The preference for the indel sites also seem to be confined to a few backbone conformations involving β-turns and helix C-caps. These are mainly associated with short loops joining the regular secondary structures that mediate a reversal in the chain direction. Rare β-turns of type I’ and II’ are also identified as preferred sites for insertions.

Nuclear Protein-Only Ribonuclease P2 Structure and Biochemical Characterization Provide Insight into the Conserved Properties of tRNA 5′ End Processing Enzymes

“…The PPR domains of PRORP1 and PRORP2 share high amino acid identity (~45 %, Supplemental Figure 3) and structural homology. As expected with paralogous proteins 37 most of the differences between PRORP1 and PRORP2 are localized in the loop regions connecting the well-conserved structural elements. Example differences include the observation that the intra-domain loop of the second PPR motif in A. thaliana PRORPs is eight amino acids longer than in a canonical PPR repeat (Supplemental Figure 4A), and the presence of a two amino acid insertion in the third motif of the PRORP2 intradomain loop that is missing in PRORP1.…”

Differential Site Accessibility Mechanistically Explains Subcellular-Specific N-Glycosylation Determinants

“…The glycosylation site solvent accessibility was determined by measuring the accessibility to the individual asparagine residues forming the glycosylation sites using NACCESS 6 ( 42 ), an accurate and frequently used solvent accessibility determination program ( 19 , 43 – 45 ). NACCESS calculates the atomic accessible area by predicting van der Waal’s interactions when a probe is rolled around on the protein surface ( 46 , 47 ).…”

Structural elucidation of estrus urinary lipocalin protein (EULP) and evaluating binding affinity with pheromones using molecular docking and fluorescence study

“…Sharing of strong structural folding and conservational local backbone amino acids were also revealed. This can help in further understanding amino acid interaction, contact energy protein of the structure, and geometric quality of the model35.…”