Prediction of potential protein-protein interaction sites from amino acid sequence. Identification of a fibrin polymerization site.
Identification of a protein-protein interaction site is an important step that has significant potential to clarify structure-function relationships of proteins and drug design. We propose here a unique predictive method to identify protein-protein interaction sites based on the observation that proline is the most common residue found in the flanking segments of interaction sites [Kini, R.M. and Evans, H.J. (1995) Biochem. Biophys. Res. Commun. 212, 1115-1124]. Accordingly, the interaction sites of proteins might be predicted directly from the amino acid sequence based on the presence of proline brackets. Using this strategy, we have predicted a polymerization site in the epitope of the Aalpha-chain of fibrinogen recognized by a monoclonal antibody, 9E9 which inhibits fibrin polymerization [Cierniewski, C.S. and Budzynski, A.Z. (1992) Biochemistry 31, 4248-4253]. The synthetic peptide comprising this predicted site inhibited the coagulation of human blood and allosterically interfered in fibrin polymerization. This is the first known allosteric polymerization site of fibrinogen. Thus the results validate the predicted site and the method for prediction. This unique predictive method should help in identifying the interaction sites of many proteins.
Kini
R M
RM
Department of Biochemistry and Molecular Biophysics, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0614, USA.
Evans
H J
HJ
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D001777:Blood Coagulation; D000939:Epitopes; D005337:Fibrin / Q000737:chemistry*; D005340:Fibrinogen / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011392:Proline / Q000737:chemistry; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D000939:Epitopes; D009842:Oligopeptides; D011108:Polymers; D011506:Proteins; D005337:Fibrin; D005340:Fibrinogen; D011392:Proline