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Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease.

Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease.

Authors :
Wischik CM
Novak M
Thøgersen HC
Edwards PC
Runswick MJ
Jakes R
Walker JE
Milstein C
Roth M
Klug A
Source :
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 1988 Jun; Vol. 85 (12), pp. 4506-10.
Publication Year :
1988

Abstract

A substantially enriched preparation of Alzheimer paired helical filaments (PHFs) has been used as a starting point for biochemical studies. Pronase treatment, which strips off adhering proteins, leaves a resistant core that is structurally intact. This has been used to raise a monoclonal antibody that decorates the filament core. The antibody has been used to follow the extraction of two peptide fragments (9.5 and 12 kDa) by immunoblotting. The link between the PHF as a morphological entity and these peptides has been established independently by photoaffinity labeling with a chemical ligand to the PHF core. Sequence analysis of these peptides was used to design oligonucleotide probes for cloning a cognate cDNA, which leads to its identification as human microtubule-associated tau protein. The sequencing of the 9.5- and 12-kDa peptides shows they are derived from a conserved region of tau containing three repeating segments. Since these fragments have been copurified with the Pronase-resistant core and are only released by subsequent steps, the corresponding part of the tau molecule must be tightly bound in the PHF core.

Details

Language :
English
ISSN :
0027-8424
Volume :
85
Issue :
12
Database :
MEDLINE
Journal :
Proceedings of the National Academy of Sciences of the United States of America
Publication Type :
Academic Journal
Accession number :
3132715
Full Text :
https://doi.org/10.1073/pnas.85.12.4506