In VitroPolymerization of Embryonic MAP-2c and Fragments of the MAP-2 Microtubule Binding Region into Structures Resembling Paired Helical Filaments*

التفاصيل البيبلوغرافية
العنوان: In VitroPolymerization of Embryonic MAP-2c and Fragments of the MAP-2 Microtubule Binding Region into Structures Resembling Paired Helical Filaments*
المؤلفون: DeTure, Michael A., Yi Zhang, Edith, Bubb, Michael R., Purich, Daniel L.
المصدر: Journal of Biological Chemistry; December 1996, Vol. 271 Issue: 51 p32702-32706, 5p
مستخلص: 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.
قاعدة البيانات: Supplemental Index
الوصف
تدمد:00219258
1083351X
DOI:10.1074/jbc.271.51.32702