Location of the binding site "b" for lateral polymerization of fibrin.

We examined the location of the binding site "b" for lateral polymerization of fibrin using two fractions of normal human fibrinogen, a high-molecular weight fraction (so-called normal fibrinogen) and a low-molecular weight fraction which lacks the C-terminal half of one of its two A alpha chains, and Gly-His-Arg-Pro, a synthetic peptide that corresponds to the N-terminal sequence of human fibrin beta chain and binds specifically to the site "b". The amounts of the synthetic peptide bound to each of the low- and high-molecular weight fractions were 1 mol/mol and 2 mol/mol, respectively. The peptide delayed the clotting of fibrinogen by blocking the site "b", but did not inhibit thrombin at all. In the presence of the peptide, the high-molecular weight fraction did not form a normal coarse clot but a fine clot which was identical to that produced by the low-molecular weight fraction. The identity of the two clots was judged from four different points: morphology, turbidity, elasticity and clotting velocity of fibrin. The results suggest that the site "b" is located within the portion of the fibrinogen molecule present in the high-molecular weight fraction, but not in the low-molecular weight fraction and that the site "b" plays an essential role in the lateral polymerization of fibrin.