Dissecting and analyzing key residues in protein‐DNA complexes

Abstract

Protein-DNA interactions are involved in various fundamental biological processes such as replication, transcription, DNA repair, and gene regulation. To understand the interaction in protein-DNA complexes, the integrative study of binding and stabilizing residues is important. In the present study, we have identified key residues that play a dual role in both binding and stability from a nonredundant dataset of 319 protein-DNA complexes. We observed that key residues are identified in very less number of complexes (29%) and only about 4% of stabilizing/binding residues are identified as key residues. Specifically, stabilizing residues have higher preference to be key residues than binding residues. These key residues include polar, nonpolar, aliphatic, aromatic, and charged amino acids. Moreover, we have analyzed and discussed the key residues in different protein-DNA complexes, which are classified based on protein structural class, function, DNA strand, and their conformations. Especially, Ser, Thr, Tyr, Arg, and Lys residues are commonly found in most of the subclasses of protein-DNA complexes. Further, we analyzed atomic contacts, which show that polar-nonpolar is more enriched than other types of contacts. In addition, the charged contacts are highly preferred in protein-DNA complexes compared with protein-protein and protein-RNA complexes. Finally, we have discussed the sequence and structural features of key residues such as conservation score, surrounding hydrophobicity, solvent accessibility, secondary structure, and long-range order. This study will be helpful to understand the recognition mechanism and structural and functional aspects of protein-DNA complexes.

Characteristics of interactions at protein segments without non-local intramolecular contacts in the Protein Data Bank

“…For example, a 20-residue segment in the Fos-Jun complex has seven Arg residues, and six of them are in contact with DNA (Fig 4E; PDB ID: 1A02). It is well known that these residues are enriched for polynucleotide-binding interfaces [25,26]. Zhang et al reported a review for structural bioinformatics studies and their analyses of amino acid propensities for interactions; this concluded that positively charged residues are favored for polynucleotide interactions [25].…”

PreDBA: A heterogeneous ensemble approach for predicting protein-DNA binding affinity

“…Therefore, based on the rule of the Nucleic Acid Database (NDB) 26 , the protein-DNA complexes are divided into three categories: I) complexes with single-stranded DNA (SS), II) complexes with duplex DNA, III) miscellaneous complexes (MISC). According to previous studies 29,30 , it has been confirmed that protein-DNA binding site residues have an essential influence on the interaction of protein and DNA. Actually, the binding site residues are believed to play essential roles in directing the binding affinity.…”

Classification of families of DNA-recognizing protein domains based on structural features of DNA-protein complexes

“…Motivation and Aim: DNA-protein interactions play a central role in such cellular processes as DNA replication, transcription, and repair [1]. Prediction of the interactions between DNA and protein is a significant but not trivial task [2].…”