Protein residues determining interaction specificity in paralogous families
Borja Pitarch1, Juan A G Ranea2,3,4, Florencio Pazos1
1Computational Systems Biology Group, Systems Biology Department, National Centre for Biotechnology (CNB-CSIC), 28049 Madrid, Spain.
Motivation:
Predicting the residues controlling a protein's interaction specificity is important not only to better understand its interactions but also to design mutations aimed at fine-tuning or swapping them as well.
Results:
In this work, we present a methodology that combines sequence information (in the form of multiple sequence alignments) with interactome information to detect that kind of residues in paralogous families of proteins. The interactome is used to define pairwise similarities of interaction contexts for the proteins in the alignment. The method looks for alignment positions with patterns of amino-acid changes reflecting the similarities/differences in the interaction neighborhoods of the corresponding proteins. We tested this new methodology in a large set of human paralogous families with structurally characterized interactions, and discuss in detail the results for the RasH family. We show that this approach is a better predictor of interfacial residues than both, sequence conservation and an equivalent 'unsupervised' method that does not use interactome information.
Availability And Implementation:
http://csbg.cnb.csic.es/pazos/Xdet/.
Supplementary Information:
Supplementary data are available at Bioinformatics online.
Related Concept Videos
Protein Families
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Protein-protein Interfaces
Protein Complexes with Interchangeable Parts
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Ligand Binding and Linkage


