A68: A Major Subunit of Paired Helical Filaments and Derivatized Forms of Normal Tau

Putative Alzheimer disease (AD)-specific proteins (A68) were purified to homogeneity and shown to be major subunits of one form of paired helical filaments (PHFs). The amino acid sequence and immunological data indicate that the backbone of A68 is indistinguishable from that of the protein tau (τ),...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1991-02, Vol.251 (4994), p.675-678
Main Authors: Virginia M.-Y. Lee, Balin, Brian J., Otvos, Laszlo, Trojanowski, John Q.
Format: Article
Language:English
Subjects:
Alzheimer Disease - metabolism
Alzheimer's disease
Amino Acid Sequence
Amino acids
Antibodies
Antibodies, Monoclonal
Biochemistry
Blotting, Western
Epitopes
Gels
Genetics
Humans
Intermediate Filaments - metabolism
Microtubule-Associated Proteins - metabolism
Molecular Sequence Data
Molecular Weight
Neurites
Neurons
Phosphates
Phosphoproteins - metabolism
Phosphorylation
Protein isoforms
Proteins
tau Proteins
Tubulin
Tubulins
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Summary:Putative Alzheimer disease (AD)-specific proteins (A68) were purified to homogeneity and shown to be major subunits of one form of paired helical filaments (PHFs). The amino acid sequence and immunological data indicate that the backbone of A68 is indistinguishable from that of the protein tau (τ), but A68 could be distinguished from normal human τ by the degree to which A68 was phosphorylated and by the specific residues in A68 that served as phosphate acceptors. The larger apparent relative molecular mass (M$_r$) of A68, compared to normal human τ, was attributed to abnormal phosphorylation of A68 because enzymatic dephosphorylation of A68 reduced its M$_r$ to close to that of normal τ. Moreover, the LysSerProVal motif in normal human τ appeared to be an abnormal phosphorylation site in A68 because the Ser in this motif was a phosphate acceptor site in A68, but not in normal human τ. Thus, the major subunits of a class of PHFs are A68 proteins and the excessive or inappropriate phosphorylation of normal τ may change its apparent M$_r$, thus transforming τ into A68.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1899488