THE C4B-BINDING PROTEIN PROTEIN-S INTERACTION IS HYDROPHOBIC IN NATURE

C4b-binding protein (C4BP) is a major regulatory molecule of the compl ement system. By forming a non covalent complex with the anticoagulant cofactor protein S (PS), it also plays an important role in blood coa gulation. C4BP is composed of one beta-chain and seven alpha-chains th at are essentially built from complement control protein (CCP)-modules . Our group has previously reported that the first (N-terminal) CCP mo dule of the beta-chain (beta CCP1) contains the entire binding site fo r protein S, We now investigate further the binding of protein S to C4 BP and show that the complex formation is essentially dependent on hyd rophobic forces with minor contribution from electrostatic interaction s. This result is in agreement with homology modeling experiments carr ied out in conjunction with inter-species sequence comparison and theo retical enumeration of potential binding sites. These methods pinpoint a solvent exposed hydrophobic cluster at the surface of the beta CCP1 module that is of crucial importance for the binding process. (C) 199 8 Elsevier Science B.V. All rights reserved.