Regions of tau implicated in the paired helical fragment core as defined by NMR.
We have studied the mature Alzheimer-like fibers of tau by fluorescence and NMR spectroscopy. Assembly of the protein into paired helical filaments after incubation with heparin at 37 degrees C was verified by electron microscopy and size-exclusion chromatography. NMR spectroscopy on these mature fibers revealed different regions of residual mobility for tau: the N-terminal domain was found to maintain solution-like dynamics and was followed by a large domain of decreasing mobility; finally the core region was distinguished by a solid-like character. Heteronuclear-NOE data indicate that the decreasing mobility is due to both a slowing down of the rapid nanosecond movements and the introduction of slower movements that lead to exchange broadening. Fluorescence spectroscopy confirmed the presence of this rigid core, and some degree of protection from hydrogen exchange for those residues was observed. Hence, our data give a more precise picture of the dynamics of tau when it is integrated into mature filaments and should provide further understanding of the molecular processes that govern aggregation.
Sillen
Alain
A
CNRS-Université de Lille 2 UMR 8525, Institut Pasteur de Lille, B.P. 245, 59019 Lille Cedex, France.
Leroy
Arnaud
A
Wieruszeski
Jean-Michel
JM
Loyens
Anne
A
Beauvillain
Jean-Claude
JC
Buée
Luc
L
Landrieu
Isabelle
I
Lippens
Guy
G
D002850:Chromatography, Gel; D006493:Heparin / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D016874:Neurofibrillary Tangles / Q000737:chemistry* / Q000648:ultrastructure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013050:Spectrometry, Fluorescence; D016875:tau Proteins / Q000737:chemistry* / Q000648:ultrastructure
D016875:tau Proteins; D006493:Heparin