Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1074/jbc.M501565200
Title (Primary) Sites of tau important for aggregation populate β-structure and bind to microtubules and polyanions
Author Mukrasch, M.D.; Biernat, J.; von Bergen, M.; Griesinger, C.; Mandelkow, E.; Zweckstetter, M.
Source Titel Journal of Biological Chemistry
Year 2005
Department PROTEOM
Volume 280
Issue 26
Page From 24978
Page To 24986
Language englisch
Abstract The aggregation of the microtubule-associated tau protein and formation of "neurofibrillary tangles" is one of the hallmarks of Alzheimer disease. The mechanisms underlying the structural transition of innocuous, natively unfolded tau to neurotoxic forms and the detailed mechanisms of binding to microtubules are largely unknown. Here we report the high-resolution characterization of the repeat domain of soluble tau using multidimensional NMR spectroscopy. NMR secondary chemical shifts detect residual -structure for 8-10 residues at the beginning of repeats R2-R4. These regions correspond to sequence motifs known to form the core of the cross--structure of tau-paired helical filaments. Chemical shift perturbation studies show that polyanions, which promote paired helical filament aggregation, as well as microtubules interact with tau through positive charges near the ends of the repeats and through the -forming motifs at the beginning of repeats 2 and 3. The high degree of similarity between the binding of polyanions and microtubules supports the hypothesis that stable microtubules prevent paired helical filament formation by blocking the tau-polyanion interaction sites, which are crucial for paired helical filament formation.
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=3632
Mukrasch, M.D., Biernat, J., von Bergen, M., Griesinger, C., Mandelkow, E., Zweckstetter, M. (2005):
Sites of tau important for aggregation populate β-structure and bind to microtubules and polyanions
J. Biol. Chem. 280 (26), 24978 - 24986 10.1074/jbc.M501565200