Details zur Publikation

Referenztyp Zeitschriften
DOI / URL Link
Titel (primär) Characterization of Alzheimer's-like paired helical filaments from the core domain of tau protein using solid-state NMR spectroscopy
Autor Andronesi, O.C.; von Bergen, M.; Biernat, J.; Seidel, K.; Griesinger, C.; Mandelkow, E.; Baldus, M.;
Journal / Serie Journal of the American Chemical Society
Erscheinungsjahr 2008
Department PROTEOM;
Band/Volume 130
Heft 18
Sprache englisch;
Abstract The polymerization of the microtubule-associated protein tau into paired helical filaments (PHFs) represents one of the hallmarks of Alzheimer's disease. We employed solid-state nuclear magnetic resonance (NMR) to investigate the structure and dynamics of PHFs formed in vitro by the three-repeat-domain (K19) of protein tau, representing the core of Alzheimer PHFs. While N and C termini of tau monomers in PHFs are highly dynamic and solvent-exposed, the rigid segment consists of three major ß-strands. Combination of through-bond and through-space ssNMR transfer methods with water-edited (15N,13C) and (13C,13C) correlation experiments suggests the existence of a fibril core that is largely built by repeat unit R3, flanked by surface-exposed units R1 and R4. Solid-state NMR, circular dichroism, and the fibrillization behavior of a K19 mutant furthermore indicate that electrostatic interactions play a central role in stabilizing the K19 PHFs.
ID 738
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=738
Andronesi, O.C., von Bergen, M., Biernat, J., Seidel, K., Griesinger, C., Mandelkow, E., Baldus, M. (2008):
Characterization of Alzheimer's-like paired helical filaments from the core domain of tau protein using solid-state NMR spectroscopy
J. Am. Chem. Soc. 130 (18), 5922 - 5928