Open AccessCrystallization and preliminary X‐ray diffraction analysis of the Fab fragment of WO2, an antibody specific for the Aβ peptides associated with Alzheimer's disease
Author(s) -
Wun Kwok S.,
Miles Luke A.,
Crespi Gabriela A. N.,
Wycherley Kaye,
Ascher David B.,
Barnham Kevin J.,
Cappai Roberto,
Beyreuther Konrad,
Masters Colin L.,
Parker Michael W.,
McKinstry William J.
Publication year - 2008
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309108011718
Subject(s) - orthorhombic crystal system , polyethylene glycol , epitope , crystallography , crystallization , chemistry , peptide , antibody , monoclonal antibody , resolution (logic) , crystal structure , biology , biochemistry , immunology , organic chemistry , artificial intelligence , computer science
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 ZnSO 4 ; they belonged to the orthorhombic space group P 2 1 2 1 2 1 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, P 2 1 2 1 2 1 , 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 P 2 1 and diffracted to 1.9 Å resolution.