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Regions of Tau Implicated in the Paired Helical Fragment Core as Defined by NMR
Author(s) -
Sillen Alain,
Leroy Arnaud,
Wieruszeski JeanMichel,
Loyens Anne,
Beauvillain JeanClaude,
Buée Luc,
Landrieu Isabelle,
Lippens Guy
Publication year - 2005
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200400452
Subject(s) - heteronuclear molecule , chemistry , nuclear magnetic resonance spectroscopy , spectroscopy , biophysics , fluorescence , fluorescence spectroscopy , crystallography , nanosecond , size exclusion chromatography , heteronuclear single quantum coherence spectroscopy , two dimensional nuclear magnetic resonance spectroscopy , stereochemistry , biochemistry , biology , laser , physics , quantum mechanics , optics , enzyme
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 °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.