Fibrinogen precursors. Order of assembly of fibrinogen chains

Hep-G2 cells, incubated with L-[35S]methionine, incorporate radioactivity into fibrinogen and several fibrinogen-related compounds. Pulse-chase experiments indicate that several of these compounds are precursors of fibrinogen and that the cells contain intracellular pools of A alpha and gamma chains which participate in the assembly of fibrinogen. The rate of synthesis of the three component chains of fibrinogen is unequal with that of the B beta chain being less than that of the A alpha and gamma chains. The sequence of events which lead to the assembly of fibrinogen was deduced by determining the appearance of the radioactive chains in each of the fibrinogen precursors and in fibrinogen at various times during a pulse-chase incubation. Fibrinogen assembly commences while nascent incomplete B beta chains are attached at polysomes. Preformed A alpha and gamma chains, drawn from the intracellular pool, combine independently to the growing B beta chains. On completion of the nascent B beta chains, newly formed B beta-A alpha and B beta-gamma complexes are released from the polysomes and enter the luminal space of the endoplasmic reticulum. Later other A alpha and gamma chains are added by ordered disulfide interaction, leading to the eventual formation of dimeric fibrinogen.