The Structural Basis of Monoclonal Antibody Alz50's Selectivity for Alzheimer's Disease Pathology*
- From the Department of Cell and Molecular Biology, Northwestern University Medical School, and the Northwestern University Institute for Neuroscience, Chicago, Illinois 60611-3008
- §To whom correspondence should be addressed: Dept. of Cell and Molecular Biology W129, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611-3008. Tel.: 312-503-0849; Fax: 312-503-7912; Email: JKuret{at}nwu.edu
Abstract
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.
Footnotes
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↵* This work was supported by National Institutes of Health Grants AG09466 (to L. I. B. and J. K.), AG09031 (to L. I. B.), and GM44806 (to J. K.). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- AD
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Alzheimer's disease
- PHF
-
paired helical filament
- TBS
-
Tris-buffered saline
- kb
-
kilobase
- HEPES
-
N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid.
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- Received August 22, 1996.
- Revision received September 20, 1996.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
