Localization of a fibrin gamma-chain polymerization site within segment Thr-374 to Glu-396 of human fibrinogen.

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Abstract
Fibrinogen fragment D1 was converted to fragment D3 by plasmic digestion. This conversion eliminates the ability of the fragment to interact with thrombin-exposed sites on fibrin monomer. Peptides released during this plasmic digestion were assayed for the presence of a polymerization site by affinity chromatography on fibrin monomer-Sepharose. A 33-residue peptide, corresponding to .gamma.-chain Thr-374 to Lys-406, bound to immobilized fibrin monomer. This peptide is a shorter variant of a previously isolated 38-residue peptide (.gamma.-chain Thr-374 to Val-411) that contains a polymerization site. The peptide mixture derived from fragment D1 was digested further with Staphylococcus aureus protease V8, and a 23-residue peptide, .gamma.-chain Thr-374 to Glu-396, carrying a polymerization site, was isolated by affinity chromatography. This 23-residue peptide inhibits the polymerization of desA-fibrinogen. A polymerization site complementary to the site exposed by removal of fibrinopeptide A is present in this segment. The localization of the polymerization site within the .gamma.-chain segment 374-396 implies that the polymerization site does not overlap with segments of the .gamma.-chain that are responsible for platelet aggregation and for Staphylococcus clumping (residues 400-411 and 397-411, respectively) or with the residues involved in factor XIIIa-catalyzed fibrin crosslinking (Gln-398 and Lys-406).