Localization of a fibrin gamma-chain polymerization site within segment Thr-374 to Glu-396 of human fibrinogen.
Horwitz B.H., Varadi A., Scheraga H.A.
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. We found that a 33-residue peptide, corresponding to gamma-chain Thr-374 to Lys-406, binds 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 [Olexa, S. A. & Budzynski, A. Z. (1981) J. Biol. Chem. 256, 3544-3549]. 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. We conclude that 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).
Proc. Natl. Acad. Sci. U.S.A. 81:5980-5984(1984) [PubMed] [Europe PMC]