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 s tep that has significant potential to clarify structure-function relat ionships of proteins and drug design. We propose here a unique predict ive method to identify protein-protein interaction sites based on the observation that proline is the most common residue found in the flank ing segments of interaction sites [Kini, R.M. and Evans, H.J. (1995) B iochem, Biophys, Res, Commun, 212, 1115-1124]. Accordingly, the intera ction sites of proteins might be predicted directly from the amino aci d sequence based on the presence of proline brackets, Using this strat egy, we have predicted a polymerization site in the epitope of the A a lpha-chain of fibrinogen recognized by a monoclonal antibody, 9E9 whic h 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 allo sterically interfered in fibrin polymerization. This is the first know n allosteric polymerization site of fibrinogen. Thus the results valid ate the predicted site and the method for prediction. This unique pred ictive method should help in identifying the interaction sites of many proteins.