Unveiling evolutionary signals in protein-protein interaction interfaces

ELIN TEPPA; DIEGO JAVIER ZEA; ARIEL CHERNOMORETZ; CRISTINA MARINO BUSLJE

Bariloche

Conferencia; 5th Argentinian Conference on Bioinfomatics and Computational Biology; 2014

Asociación Argentina de Bioinformática y Biología Computacional

Protein-protein interactions are involved in most cellular processes. The study of protein interactions from an evolu-tionary perspective is challenging, since it is difficult to distinguish evolutionary constraints due to protein structureand function preservation from those that arise due to interaction. The description and detection of evolutionarysignals in protein-protein interactions is currently a very active field of research. Interacting residues are involved ininter-molecular interactions and they are structurally and functionally constrained, and therefore subject to a selec-tion pressure that could be detected in homologous sequences. However residue conservation within the interface isfar from obvious in many cases and the signal is usually weak. One reason is that the evolutionary pressure is nothomogeneous within an interface (1). Also the coevolutionary signal between residues has been explored for detectinginteracting residues with limited success (2). A decomposition of the interacting interface has been proposed wherethere is a core of buried residues, surrounded by a rim of residues whose atoms remain with some solvent accessibility(3,4). From a functional point of view, residues of interface core and rim have different contributions to the bindingenergy and consequently different selection pressures (5).Here we present a detailed study on protein-protein interaction using a comprehensive dataset of biological unit com-plexes (6). We dissected each interacting unit into four region: protein core (PC), protein surface (PS), interactingcore (IC) and interacting rim (IR) based on the delta solvent accessibility upon complex formation and the relativesolvent accessibility in the complex. Results show that there is no substantial difference between PC and IC, andPS and IR regions regarding conservation and coevolution. Also we have found that a coevolutionary derived mea-sure (cMI) (7) displays a greater difference between IC and IR than residue conservation (see Figure 1). Regardingconservation and coevolution signals on residues involved in different number of interfaces, we have found that theirconservation increases with the number of interacting partners while their cMI score decreases (see Figure 2).Sequence analysis ID:40 Poster Sessionconservation and coevolution signals on residues involved in different number of interfaces, we have found that theirconservation increases with the number of interacting partners while their cMI score decreases (see Figure 2)References1.Guharoy M, Chakrabarti P. Conserved residue clusters at protein-protein interfaces and their use in binding site identifi-cation. BMC Bioinformatics. 2010;11:286.2.Mintseris J, Weng Z. Structure, function, and evolution of transient and obligate protein-protein interactions. Proc NatlAcad Sci U S A. 2 de agosto de 2005;102(31):10930-5.3.Bogan AA, Thorn KS. Anatomy of hot spots in protein interfaces. J Mol Biol. 3 de julio de 1998;280(1):1-9.4.Lo Conte L, Chothia C, Janin J. The atomic structure of protein-protein recognition sites. J Mol Biol. 5 de febrero de1999;285(5):2177-98.5.Guharoy M, Chakrabarti P. Conservation and relative importance of residues across protein- protein interfaces. Proc NatlAcad Sci U S A. 25 de octubre de 2005;102(43):15447-52.6.Bickerton GR, Higueruelo AP, Blundell TL. Comprehensive, atomic-level characterization of structurally characterizedprotein-protein interactions: the PICCOLO database. BMC Bioinformatics. 29 de julio de 2011;12(1):313.7.Marino Buslje C, Teppa E, Di Doménico T, Delfino JM, Nielsen M. Networks of High Mutual Information Define theStructural Proximity of Catalytic Sites: Implications for Catalytic Residue Identification. PLoS Comput Biol. 4 denoviembre de 2010;6(11):e1000978