CRYSTAL-STRUCTURE OF A RECOMBINANT ALPHA-C-E DOMAIN FROM HUMAN FIBRINOGEN-420

The crystal structure of a recombinant alpha(E)C domain from human fib rinogen-420 has been determined at a resolution of 2.1 Angstrom. The p rotein, which corresponds to the carboxyl domain of the alpha(E) chain , was expressed in and purified from Pichia pastoris cells. Felicitous ly, during crystallization an amino-terminal segment was removed, appa rently by a contaminating protease, allowing the 201-residue remaining parent body to crystallize. An x-ray structure was determined by mole cular replacement, The electron density was clearly defined, partly as a result of averaging made possible by there being eight molecules in the asymmetric unit related by noncrystallographic symmetry (P1 space group), Virtually all of an asparagine-linked sugar cluster is presen t. Comparison with structures of the beta- and gamma-chain carboxyl do mains of human fibrinogen revealed that the binding cleft is essential ly neutral and should not bind Gly-Pro-Arg or Gly-His-Arg peptides of the sort bound by those other domains. Nonetheless, the cleft is clear ly evident, and the possibility of binding a carbohydrate ligand like sialic acid has been considered.