Conformational changes in fragments D and double-D from human fibrin(ogen)upon binding the peptide ligand Gly-His-Arg-Pro-amide

The structure of fragment double-D from human fibrin has been solved in the presence and absence of the peptide ligands that simulate the two knobs ex posed by the removal of fibrinopeptides A and B, respectively. All told, si x crystal structures have been determined, three of which are reported here for the first time: namely, fragments D and double-D with the peptide GHRP am alone and double-D in the absence of any peptide ligand. Comparison of t he structures has revealed a series of conformational changes that are brou ght about by the various knob-hole interactions. Of greatest interest is a moveable "flap" of two negatively charged amino acids (Glu(beta 397) and As p(beta 398)) whose side chains are pinned back to the coiled coil with a ca lcium atom bridge until GHRPam occupies the beta-chain pocket. Additionally , in the absence of the peptide ligand GPRPam, GHRPam binds to the gamma-ch ain pocket, a new calcium-binding site being formed concomitantly.