The structural basis of monoclonal antibody Alz50's selectivity for Alzheimer's disease pathology.
The epitope on tau protein recognized by the monoclonal antibody Alz50 was defined through internal deletion mutagenesis and quantified by affinity measurements. The epitope is discontinuous and requires both a previously identified N-terminal segment and the microtubule binding region for efficient binding of Alz50. The interaction between these regions is consistent with an intramolecular reaction mechanism, suggesting that Alz50 binding depends on the conformation of individual tau monomers. The results suggest that tau adopts a distinct conformation when polymerized into filaments and that this conformation is recognized selectively by Alz50.
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Department of Cell and Molecular Biology, Northwestern University Medical School, and the Northwestern University Institute for Neuroscience, Chicago, Illinois 60611-3008, USA. JKuret@nwu.edu
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D000544:Alzheimer Disease / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001665:Binding Sites; D018604:Epitope Mapping; D006801:Humans; D046911:Macromolecular Substances; D008870:Microtubules / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000276:immunology; D011487:Protein Conformation; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D016875:tau Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D046911:Macromolecular Substances; D016875:tau Proteins