Analysing six types of protein-protein interfaces.
Non-covalent residue side-chain interactions occur in many different types of proteins and facilitate many biological functions. Are these differences manifested in the sequence compositions and/or the residue-residue contact preferences of the interfaces? Previous studies analysed small data sets and gave contradictory answers. Here, we introduced a new data-mining method that yielded the largest high-resolution data set of interactions analysed. We introduced an information theory-based analysis method. On the basis of sequence features, we were able to differentiate six types of protein interfaces, each corresponding to a different functional or structural association between residues. Particularly, we found significant differences in amino acid composition and residue-residue preferences between interactions of residues within the same structural domain and between different domains, between permanent and transient interfaces, and between interactions associating homo-oligomers and hetero-oligomers. The differences between the six types were so substantial that, using amino acid composition alone, we could predict statistically to which of the six types of interfaces a pool of 1000 residues belongs at 63-100% accuracy. All interfaces differed significantly from the background of all residues in SWISS-PROT, from the group of surface residues, and from internal residues that were not involved in non-trivial interactions. Overall, our results suggest that the interface type could be predicted from sequence and that interface-type specific mean-field potentials may be adequate for certain applications.
Ofran
Yanay
Y
CUBIC, Department of Biochemistry and Molecular Biophysics, Columbia University, 650 West 168th Street BB217, New York, NY 10032, USA. yo135@columbia.edu
Rost
Burkhard
B
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis / Q000737:chemistry; D030562:Databases, Protein; D008433:Mathematics; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
D000596:Amino Acids; D011506:Proteins