title: Nuclear magnetic resonance spectroscopy characterization of interaction of Tau with DNA and its regulation by phosphorylation.
abstract: The capacity of endogenous Tau to bind DNA has been recently identified in neurons under physiological or oxidative stress conditions. Characterization of the protein domains involved in Tau-DNA complex formation is an essential first step in clarifying the contribution of Tau-DNA interactions to neurological biological processes. To identify the amino acid residues involved in the interaction of Tau with oligonucleotides, we have characterized a Tau-DNA complex using nuclear magnetic resonance spectroscopy. Interaction of an AT-rich or GC-rich 22 bp oligonucleotide with Tau showed multiple points of anchoring along the intrinsically disordered Tau protein. The main sites of contact characterized here correspond to the second half of the proline-rich domain (PRD) of Tau and the R2 repeat in the microtubule binding domain. This latter interaction site includes the PHF6* sequence known to govern Tau aggregation. The characterization was pursued by studying the binding of phosphorylated forms of Tau, displaying multiple phosphorylation sites mainly in the PRD, to the same oligonucleotide. No interaction of phospho-Tau with the oligonucleotide was detected, suggesting that pathological Tau phosphorylation could affect the physiological function of Tau mediated by DNA binding.
authors.affiliation: UMR8576 CNRS-Lille University , 59655 Villeneuve d'Ascq, France.
authors.forename: Haoling
authors.initials: H
authors.lastname: Qi
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Cantrelle
authors.forename: Houda
authors.initials: H
authors.lastname: Benhelli-Mokrani
authors.forename: Caroline
authors.initials: C
authors.lastname: Smet-Nocca
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
authors.forename: Guy
authors.initials: G
authors.lastname: Lippens
authors.forename: Eliette
authors.initials: E
authors.lastname: Bonnefoy
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Galas
authors.forename: Isabelle
authors.initials: I
authors.lastname: Landrieu
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D016875:tau Proteins; D004247:DNA