Crystallization and preliminary X-ray diffraction analysis of the Fab fragment of WO2, an antibody specific for the Aβ peptides associated with Alzheimer's disease

The murine monoclonal antibody WO2 specifically binds the N-terminal region of the amyloid β peptide (Aβ) associated with Alzheimer's disease. This region of Aβ has been shown to be the immunodominant B-cell epitope of the peptide and hence is considered to be a basis for the development of immunotherapeutic strategies against this prevalent cause of dementia. Structural studies have been undertaken in order to characterize the molecular basis for antibody recognition of this important epitope. Here, details of the crystallization and X-ray analysis of the Fab fragment of the unliganded WO2 antibody in two crystal forms and of the complexes that it forms with the truncated Aβ peptides Aβ_1–16 and Aβ_1–28 are presented. These crystals were all obtained using the hanging-drop vapour-diffusion method at 295 K. Crystals of WO2 Fab were grown in polyethylene glycol solutions containing ZnSO₄; they belonged to the orthorhombic space group P2₁2₁2₁ and diffracted to 1.6 Å resolution. The complexes of WO2 Fab with either Aβ_1–­16 or Aβ_1–28 were cocrystallized from polyethylene glycol solutions. These two complex crystals grew in the same space group, P2₁2₁2₁, and diffracted to 1.6 Å resolution. A second crystal form of WO2 Fab was grown in the presence of the sparingly soluble Aβ_1–42 in PEG 550 MME. This second form belonged to space group P2₁ and diffracted to 1.9 Å resolution.