Conservation of inter-residue interactions and prediction of folding rates of domain repeats

Abstract

Domains are the main structural and functional units of larger proteins. They tend to be contiguous in primary structure and can fold and function independently. It has been observed that 10-20% of all encoded proteins contain duplicated domains and the average pairwise sequence identity between them is usually low. In the present study, we have analyzed the structural similarity between domain repeats of proteins with known structures available in the Protein Data Bank using structure-based inter-residue interaction measures such as the number of long-range contacts, surrounding hydrophobicity, and pairwise interaction energy. We used RADAR program for detecting the repeats in a protein sequence which were further validated using Pfam domain assignments. The sequence identity between the repeats in domains ranges from 20 to 40% and their secondary structural elements are well conserved. The number of long-range contacts, surrounding hydrophobicity calculations and pairwise interaction energy of the domain repeats clearly reveal the conservation of 3-D structure environment in the repeats of domains. The proportions of mainchain-mainchain hydrogen bonds and hydrophobic interactions are also highly conserved between the repeats. The present study has suggested that the computation of these structure-based parameters will give better clues about the tertiary environment of the repeats in domains. The folding rates of individual domains in the repeats predicted using the long-range order parameter indicate that the predicted folding rates correlate well with most of the experimentally observed folding rates for the analyzed independently folded domains.

Identification and Analysis of Long Repeats of Proteins at the Domain Level

“…In this study, we used the RADAR program for internal repeat detection, since it often detects both tandem and interspersed repeats in larger size. Our earlier studies for repeats analysis (Mary Rajathei and Selvaraj, 2013; Mary et al, 2015) have shown the ability of RADAR to detect repeats of length > 50 that are structurally similar and conserved in a 3D structure environment. Further, the sensitivity and accuracy of RADAR repeats, by comparison with Pfam, indicate good coverage, accurate alignments, and reasonable repeat borders (Heger and Holm, 2000).…”

“…Our analysis of sequence repeats of the proteins with known 3D structures in the PDB (Berman et al, 2014) has shown that they retain similar folds in spite of divergences, in order to conserve the structure and function of the proteins and, repeats that are in the single/two domains from the same family contain conserved motifs for the function of the proteins (Mary Rajathei and Selvaraj, 2013). Further, the conservation of inter-residues interactions in domain repeats have been analyzed in terms of long-range contact, surrounding hydrophobicity and pair-wise interaction energy (Mary et al, 2015). A database IR-PDB for repeats in the sequence of the proteins in the PDB has been developed for the analysis of impact of repeats in proteins (Selvaraj and Rajathei, 2017).…”

Structure-Based Drug Designing Studies Towards Exploring the Potential Anticancer Activity of Selected Phytocompounds Against Histone Deacetylase 10 Protein

“…Conservation of inter-residue interactions will be helpful to predict the folding rate of domain and repeats in proteins [51]. It has been found that, during the process of protein folding, the amino acid residues along the polypeptide chain interact with each other to form the stable native structure.…”

Sequence and structural analysis of fibronectin‐binding protein reveals importance of multiple intrinsic disordered tandem repeats

“…Some novel tandem repeats (a region of the protein sequence that occurs more than once in tandem) are identified in cell surface proteins which suggest that sequence patterns in the repeats involve a mechanism to provide a regular array for spatial arrangement, structural packing, or interactions with target molecules . Interestingly, many reports in the literature deal with the functional consequences of sequence repeats, and it was shown that most of the sequence repeats are unstructured or intrinsically disordered . Intrinsically disordered regions (IDRs) are important components of proteins which help to undertake different interactions with different consequence .…”

“…22,23 Interestingly, many reports in the literature deal with the functional consequences of sequence repeats, and it was shown that most of the sequence repeats are unstructured or intrinsically disordered. [24][25][26] Intrinsically disordered regions (IDRs) are important components of proteins which help to undertake different interactions with different consequence. 27 IDRs are polypeptide segments without sufficient hydrophobic amino acid residues to form folded compact structure; instead, they are flexible and mainly made up of polar or charged amino acids.…”