Carboxy-terminal amino acid sequence of a human fibrinogen gamma-chain variant (gamma').

A normal human fibrinogen gamma-chain variant, termed gamma', is larger than the gamma chain (51 500 vs. 49 500) due to an extended COOH-terminal sequence. The extended COOH-terminal cyanogen bromide peptide (CNBr e') was isolated by high-pressure liquid chromatography, and its amino acid sequence was determined. Comparison with the corresponding COOH-terminal gamma-chain peptide (CNBr e) showed that the last four amino acids of the gamma chain were replaced in gamma' chains by a 20-residue fragment rich in aspartic and glutamic acids, having the sequence Val-Tyr-Pro-Glu-His-Pro-Ala-Glx-Thr-Glx-Tyr-Asx-Ser-Leu-Arg-Pro-Glx-Asx-Asx-Leu . Mutant gamma chains (gamma Paris I) from a congenitally dysfunctional fibrinogen molecule (fibrinogen Paris 1) express both gamma and gamma' features, suggesting that both gamma and gamma' chains are produced from a single gene. If this suggestion is correct, the observed differences in amino acid sequence could be explained by the existence of different mRNAs for gamma and gamma' chains, respectively, which are transcribed from one gene by differential RNA splicing.