Crystal Structure of Fragment Double-D from Human Fibrin with Two Different Bound Ligands,

Abstract

Factor XIII-cross-linked fragment D (double-D) from human fibrin was crystallized in the presence of two different peptide ligands and the X-ray structure determined at 2.3 Å. The peptide Gly-Pro-Arg-Pro-amide, which is an analogue of the knob exposed by the thrombin-catalyzed removal of fibrinopeptide A, was found to reside in the γ-chain holes, and the peptide Gly-His-Arg-Pro-amide, which corresponds to the β-chain knob, was found in the homologous β-chain holes. The structure shows for the first time that the β-chain knob does indeed bind to a homologous hole on the β-chain. The γ- and β-chain holes are structurally very similar, and it is remarkable they are able to distinguish between these two peptides that differ by a single amino acid. Additionally, we have found that the β-chain domain, like its γ-chain counterpart, binds calcium.