title: Regions of tau implicated in the paired helical fragment core as defined by NMR.
abstract: 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.
authors.affiliation: CNRS-Université de Lille 2 UMR 8525, Institut Pasteur de Lille, B.P. 245, 59019 Lille Cedex, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Sillen
authors.forename: Arnaud
authors.initials: A
authors.lastname: Leroy
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Wieruszeski
authors.forename: Anne
authors.initials: A
authors.lastname: Loyens
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Beauvillain
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
authors.forename: Isabelle
authors.initials: I
authors.lastname: Landrieu
authors.forename: Guy
authors.initials: G
authors.lastname: Lippens
mesh_terms: 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
chemical_list: D016875:tau Proteins; D006493:Heparin