In vitro polymerization of embryonic MAP-2c and fragments of the MAP-2 microtubule binding region into structures resembling paired helical filaments.
The microtubule-associated protein Tau is widely regarded as the principal component of paired helical filaments comprising Alzheimer neurofibrillary tangles. Tau fragments containing the non-identical repeat region formed structures resembling paired helical filaments (Schweers, O., Mandelkow, M., Biernat, J., and Mandelkow, E. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 8463-8467). MAP-2, the other structurally related neuronal microtubule-associated protein, has not been implicated in paired helical filament formation. We now describe the assembly of paired helical filament-like structures from MAP-2 polypeptides containing only 100 residues. A dimeric species, stabilized by an interchain disulfide, appears to be involved in the assembly reaction. We also investigated the polymerization of embryonic MAP-2c, which, except for its microtubule binding region, is structurally distinct from Tau. Full-length MAP-2c formed paired helical filament-like polymers. Polymerized MAP-2c and the microtubule binding region fragment readily bound thioflavin-S, a dye that stains paired helical filaments in the histochemical diagnosis of Alzheimer's disease. Our unprecedented finding that a small MAP-2 microtubule binding region fragment and MAP-2c can form structures resembling straight filaments or Pronase-treated paired helical filaments raises fundamental questions concerning the role of MAP-2 in the pathobiology of Alzheimer disease.
DeTure
M A
MA
Department of Biochemistry and Molecular Biology, University of Florida College of Medicine Health Science Center, Gainesville, FL 32610-0245, USA.
Zhang
E Y
EY
Bubb
M R
MR
Purich
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DL
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D016874:Neurofibrillary Tangles / Q000648:ultrastructure; D010446:Peptide Fragments; D011485:Protein Binding; D051381:Rats; D011994:Recombinant Proteins; D012091:Repetitive Sequences, Nucleic Acid; D013050:Spectrometry, Fluorescence
D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins