Analysis of proteins commonly requires a partition of their structure into regions such as surface, interior, or interface. Despite the frequent use of such categorization, no consensus definition seems to exist. We thus aim at providing a definition that is general, simple to implement, and that yields new biological insights. Our analysis relies on 397, 196 and 701 protein structures from E. coli, S. cerevisiae and H. sapiens respectively, and our conclusions are consistent across all three species. We find that 25% relative accessible surface area best segregates amino acids at the interior and surface. We further use this value to extend the core-rim model of protein-protein interfaces, and introduce a third region that we call support. Interface core, rim and support regions contain similar numbers of residues on average, but core residues contribute over two-thirds of the contact surface. The amino acid composition of each region remains similar across different organisms and interface types. The interface core composition is intermediate between surface and interior, but the compositions of the support and rim are virtually identical to those of the interior and surface respectively. The support and rim could thus "pre-exist" in proteins, and evolving a new interaction could require mutations to form an interface core only. Using the interface regions defined, we show through simulations that only two substitutions are necessary to shift the average composition of a 1000A(2) surface patch involving ~28 residues to that of an equivalent interface. Our analysis and conclusions will help understand the notion of promiscuity in protein-protein interaction networks.CI - Copyright (c) 2010. Published by Elsevier Ltd.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Annotation Extension||Reference|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Assay||Construct||Conditions||Strain Background||Reference|