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Preparation, Crystallization and Preliminary X-Ray Analysis of the Fab Fragment of Monoclonal Antibody MN423, Revealing the Structural Aspects of Alzheimer's Paired Helical Filaments

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Abstract:

Monoclonal antibody (mAb) MN423 recognizes Alzheimer's disease specific conformation of tau protein assembled into paired helical filaments (PHF). Since the three-dimensional structure of PHF is currently unavailable, the structure of MN423 binding site could provide important information about PHF conformation with the consequences for the Alzheimer's disease prevention and cure. Fab fragment of MN423 was prepared and purified. We have identified two different conditions for crystallization of the Fab fragment that yielded two crystal forms. They diffracted to 3.0 and 1.6 Å resolution with four and one molecule in the asymmetric unit, respectively. Both crystal forms belonged to the space group P21 with unit cell parameters a = 76.4 Å, b = 138.4 Å, c = 92.4 Å, β = 101.9∞, and a = 71.5 Å, b = 36.8 Å, c = 85.5 Å , β = 113.9∞.





Keywords: Alzheimer's disease; Crystallization; Fab fragment; Paired Helical Filaments; X-ray data

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986606778256180

Affiliations: Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, 845 10 Bratislava, Slovakia.

Publication date: September 1, 2006

More about this publication?
  • Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.
ben/ppl/2006/00000013/00000009/art00010
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