title: Structural similarity enhances interaction propensity of proteins.
abstract: We study statistical properties of interacting protein-like surfaces and predict two strong, related effects: (i) statistically enhanced self-attraction of proteins; (ii) statistically enhanced attraction of proteins with similar structures. The effects originate in the fact that the probability to find a pattern self-match between two identical, even randomly organized interacting protein surfaces is always higher compared with the probability for a pattern match between two different, promiscuous protein surfaces. This theoretical finding explains statistical prevalence of homodimers in protein-protein interaction networks reported earlier. Further, our findings are confirmed by the analysis of curated database of protein complexes that showed highly statistically significant overrepresentation of dimers formed by structurally similar proteins with highly divergent sequences ("superfamily heterodimers"). We suggest that promiscuous homodimeric interactions pose strong competitive interactions for heterodimers evolved from homodimers. Such evolutionary bottleneck is overcome using the negative design evolutionary pressure applied against promiscuous homodimer formation. This is achieved through the formation of highly specific contacts formed by charged residues as demonstrated both in model and real superfamily heterodimers.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Lukatsky
authors.forename: B E
authors.initials: BE
authors.lastname: Shakhnovich
authors.forename: J
authors.initials: J
authors.lastname: Mintseris
authors.forename: E I
authors.initials: EI
authors.lastname: Shakhnovich
mesh_terms: D000596:Amino Acids; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D030562:Databases, Protein; D019281:Dimerization; D019143:Evolution, Molecular; D008958:Models, Molecular; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D011506:Proteins