The Binding Mode of a Tau Peptide with Tubulin

Harindranath Kadavath, Yunior Cabrales Fontela, Mariusz Jaremko, Lukasz Jaremko, Kerstin Overkamp, Jacek Biernat, Eckhard Mandelkow, Markus Zweckstetter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The microtubule-associated protein Tau promotes the polymerization of tubulin and modulates the function of microtubules. As a consequence of the dynamic nature of the Tau–tubulin interaction, the structural basis of this complex has remained largely elusive. By using NMR methods optimized for ligand–receptor interactions in combination with site-directed mutagenesis we demonstrate that the flanking domain downstream of the four microtubule-binding repeats of Tau binds competitively to a site on the α-tubulin surface. The binding process is complex, involves partial coupling of different interacting regions, and is modulated by phosphorylation at Y394 and S396. This study strengthens the hypothesis of an intimate relationship between Tau phosphorylation and tubulin binding and highlights the power of the INPHARMA NMR method to characterize the interaction of peptides derived from intrinsically disordered proteins with their molecular partners.

Original languageEnglish (US)
Pages (from-to)3246-3250
Number of pages5
JournalAngewandte Chemie - International Edition
Volume57
Issue number12
DOIs
StatePublished - Mar 12 2018

Keywords

  • NMR spectroscopy
  • Tau protein
  • structure elucidation
  • tubulin

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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