Fragment D structure is altered in the presence of Aβ42. The fragment D crystals soaked with Aβ42 were analyzed by X-ray crystallography. (A) Brightfield (left) and UV fluorescence (right) images of fragment D crystals, indicating crystals are proteinaceous. (B) Left, Brightfield image of a fragment D crystal that had been subjected to soaking in TAMRA-Aβ42 followed by extensive washing. Right, Persistent red fluorescence after washing indicated that TAMRA-Aβ42 was binding within the crystal. (C) Unit cell dimensions of published (1FZA), nonsoaked, and Aβ42-soaked fragment D crystals. (D) Diagram of human fibrinogen with fragment D (FD) marked with a box. The location of altered structure in Aβ42-soaked fragment D crystals is indicated by the solid pink line. Superimposed 2Fo-Fc maps from nonsoaked (yellow; Rwork/Rfree = 0.24/0.33) and Aβ42-soaked (teal; Rwork/Rfree = 0.28/0.39) fragment D crystals with coordinates of nonsoaked crystals. Human fibrinogen schematic was generated from PDB file 3GHG.²¹ (E) Protein backbone diagram showing the shift of the β384-393 loop from nonsoaked fragment D (pink) to b-hole peptide (GHRP)-bound (1FZG; green) fragment D and Aβ42-soaked fragment D (blue). GHRP, Gly-His-Arg-Pro-amide peptide.