Evidence of intramolecular cross-linked A alpha.gamma chain heterodimers in plasma fibrinogen.

A peptide band of approximately 105 kDa migrating near the gamma dimer position of disulfide bond reduced human plasma fibrinogen prepared from fresh single donor or outdated plasma was identified by SDS-PAGE. The band, amounting to approximately 2% of the total A alpha/gamma chain population, was thrombin and plasmin sensitive and reacted with antibodies to A alpha or gamma chains but not with antibodies to B beta chains, plasminogen, or factor XIII. Amino acid sequencing revealed a double sequence corresponding to that of A alpha and gamma chains, indicating that the band consists of covalently cross-linked A alpha.gamma chain heterodimers. A alpha.gamma heterodimers were identified as a component of monomeric fibrinogen by two-dimensional SDS-PAGE and by SDS-PAGE analysis of the monomer fraction isolated by gel sieving chromatography, thus indicating that A alpha.gamma heterodimers arise by intramolecular A alpha/gamma chain cross-linking.