Self-assembly of the brain MAP-2 microtubule-binding region into polymeric structures resembling Alzheimer filaments.
The neuronal microtubule-associated protein known as MAP-2 has not been considered to be a subunit of paired helical filaments (PHFs) in neurofibrillary tangles seen in Alzheimer's Disease. We now describe the assembly of paired helical filament-like structures from MAP-2's 203-residue microtubule-binding region (MTBR). SDS gel electrophoresis and equilibrium ultracentrifugation suggest that a dimeric form, cross-linked by an interchain disulfide, is involved in polymerization. MAP-2 MTBR polymers bind thioflavin-S, a dye used to histochemically localize Alzheimer neurofibrillary tangles. Our finding that PHF-like structures assemble from a MAP-2 fragment raises new questions about MAP-2's role in the etiology of Alzheimer's Disease.
Zhang
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Department of Biochemistry & Molecular Biology, College of Medicine, University of Florida, Gainesville 32610-0245, USA.
DeTure
M A
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Bubb
M R
MR
Caviston
T L
TL
Erdos
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Whittaker
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SD
Purich
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D000544:Alzheimer Disease / Q000209:etiology / Q000473:pathology*; D000595:Amino Acid Sequence; D000818:Animals; D052160:Benzothiazoles; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D005456:Fluorescent Dyes / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D011108:Polymers / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism / Q000648:ultrastructure; D013844:Thiazoles / Q000378:metabolism
D052160:Benzothiazoles; D005456:Fluorescent Dyes; D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; D011108:Polymers; D011994:Recombinant Proteins; D013844:Thiazoles; C009462:thioflavin T