Nuclear Magnetic Resonance Spectroscopy Characterization of Interaction of Tau with DNA and Its Regulation by Phosphorylation

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 ne...

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Bibliographic Details
Published in:Biochemistry (Easton) 2015-02, Vol.54 (7), p.1525-1533
Main Authors: Qi, Haoling, Cantrelle, François-Xavier, Benhelli-Mokrani, Houda, Smet-Nocca, Caroline, Buée, Luc, Lippens, Guy, Bonnefoy, Eliette, Galas, Marie-Christine, Landrieu, Isabelle
Format: Article
Language:English
Subjects:
Binding Sites
Biochemistry
Biochemistry, Molecular Biology
DNA - chemistry
DNA - metabolism
Life Sciences
Nuclear Magnetic Resonance, Biomolecular
Phosphorylation
Protein Binding
Protein Interaction Domains and Motifs
Recombinant Proteins - chemistry
Recombinant Proteins - metabolism
tau Proteins - chemistry
tau Proteins - metabolism
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Summary: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.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi5014613