Human platelet fibrinogen gamma chain structure.
Human plasma fibrinogen is produced by liver parenchymal cells. Such molecules contain two classes of gamma-chains (gamma A, gamma'), which differ with respect to their COOH-terminal sequences. When fibrin is crosslinked in the presence of factor XIIIa and Ca2+, three types of gamma-dimer are formed (gamma A-gamma A; gamma A-gamma'; gamma'-gamma'). A separate fibrinogen pool is located in platelet alpha-granules. We analyzed this fibrinogen to determine whether gamma'-chains were present to the same extent (7%) that they are found in plasma fibrinogen. Electrophoretic analysis (Laemmli system) of reduced samples of the clot that formed subsequent to release of fibrinogen from thrombin-stimulated washed platelets, revealed a single crosslinked gamma-dimer band in the gamma A-gamma A position. Material collected into EDTA-containing buffer and subsequently crosslinked in the presence of added factor XIII and Ca2+ also revealed a gamma A-gamma A dimer band. This finding was further investigated by Western blotting of reduced gel specimens that had been reacted with an anti-gamma-chain antibody followed by 125I-labeled protein A. A single type of gamma-chain, gamma A, was present in the fibrinogen from a Triton X-100 or 10 M urea platelet lysate, or in noncrosslinked fibrin obtained from thrombin-treated platelets. Crosslinked reduced fibrin from thrombin-treated platelets or that prepared from the Triton lysate revealed a single type of gamma-dimer, gamma A-gamma A. We conclude that there are no gamma'-chains (less than 1%) in platelet fibrinogen. This structural difference from hepatic fibrinogen probably results from differences in the processing and/or regulation of the fibrinogen gamma-chain gene in megakaryocytes.
D000347:Afibrinogenemia / Q000097:blood / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000032:analysis*; D055598:Chemical Phenomena; D002621:Chemistry; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000235:genetics; D006801:Humans; D011487:Protein Conformation; D011817:Rabbits
D003432:Cross-Linking Reagents; D005338:Fibrin Fibrinogen Degradation Products; C027539:fibrinopeptides gamma; D005340:Fibrinogen