Structure of the fibrinogen gamma-chain integrin binding and factor XIIIa cross-linking sites obtained through carrier protein driven crystallization

The human fibrinogen gamma-chain C-terminaI segment functions as the platel et integrin binding site as well as the Factor XIIIa cross-linking substrat e and thus plays an important role in blood clot formation and stabilizatio n. The three-dimensional structure of this segment has been determined usin g carrier protein driven crystallization. The C-terminal segment, gamma-(39 8-411), was attached to a linker sequence at the C-terminus of glutathione S-transferase and the structure of this fusion protein determined at 1.8 An gstrom resolution. Functional studies of the chimeric protein demonstrate t hat the fibrinogen sequence in the presence of the carrier protein retains its specific functions as ligand for platelet integrin alpha(IIb)beta 3 (gp IIb/IIIa) and as a cross-linking substrate for Factor XIIIa. The structure obtained for the fibrinogen gamma-chain segment is not affected by crystal packing and can provide the missing links to the recently reported model of cross-linked fibrin.