High Molecular Weight Derivatives of Human Fibrinogen Produced by Plasmin

Abstract

The NH2-terminal amino acid residues of the plasmin derivatives of human fibrinogen (Fragments X, Y, D, and E) were determined and compared with those of undigested fibrinogen. Fibrinogen and Fragments X (mol wt 260,000) and Y (mol wt 155,000) had primarily alanine and tyrosine NH2-terminal residues. Fragment E (mol wt 50,000) also had alanine and tyrosine and in addition contained smaller amounts of glycine and valine residues. Fragment D (mol wt 85,000) had a clearly different complement of NH2-terminal residues, aspartic acid, methionine and valine, and probably derives from the COOH-terminal part of the parent fibrinogen molecule. That the NH2-terminal region of the fibrinogen molecule is present in Fragments X, Y, and E was confirmed by direct comparison of Fragments D and E with the NH2-terminal disulfide knot (mol wt 57,000), a chemical derivative of fibrinogen that contains the NH2-terminal region of fibrinogen, including fibrinopeptides A and B. Fragment E showed striking similarity of NH2-terminal amino acid residues, cysteine content, and antigenic determinants with the NH2-terminal disulfide knot. Thus, a derivative formed by proteolytic degradation of fibrinogen, Fragment E, has been shown to be virtually identical with a derivative formed by chemical degradation, the NH2-terminal disulfide knot. These data are consistent with the hypothesis of asymmetrical proteolysis of fibrinogen by plasmin, retaining the NH2-terminal region of the fibrinogen molecule relatively intact in Fragments X, Y, and E.