Binding of Alz 50 depends on Phe8 in tau synthetic peptides and varies between native and denatured tau proteins

Brain Research
H Ksiezak-RedingP Davies

Abstract

Alz 50 is a monoclonal antibody that in Western blotting analysis recognizes both normal tau as well as hyperphosphorylated tau proteins associated with paired helical filaments (PHF-tau) in Alzheimer disease (AD). Within tissue sections of AD brain, however, Alz 50 immunolabels only PHF, which suggests that the antibody recognizes a conformational epitope. Using competitive enzyme-linked immunosorbent assay, we demonstrate that Alz 50 binds to tau synthetic peptides with low affinity (KD between 0.27 to 2.7 x 10(-5) M) and that the binding is specific for the RQEF sequence corresponding to N-terminal residues 5-8 of tau. The Alz 50 epitope appears to be largely dependent on Phe8, a strongly hydrophobic amino acid residue, since the substitution of Phe8 with Ala8 in the synthetic peptide abolishes Alz 50 binding. The effects of tau conformation on Alz 50 binding were studied with various normal tau proteins with either low or high phosphate content (adult vs. fetal) and PHF-tau proteins. The normal tau fractions were isolated from both adult and fetal human brains using affinity chromatography (native form) and heat/perchloric acid treatments (denatured form). PHF-tau was isolated as Sarcosyl-insoluble fraction. With competitiv...Continue Reading

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Citations

Dec 20, 1996·The Journal of Biological Chemistry·G CarmelJ Kuret
Nov 1, 2000·Cell Motility and the Cytoskeleton·H Ksiezak-RedingD W Dickson
Jan 16, 1999·Journal of Neuroscience Research·L S Yang, H Ksiezak-Reding
Jul 22, 1998·Progress in Neurobiology·B H AndertonC Weaver
May 12, 2007·Biochemical and Biophysical Research Communications·Hitomi UenoAkihiko Takashima

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