Folding of the Tau Protein on Microtubules

Angew Chem Int Ed Engl. 2015 Aug 24;54(35):10347-51. doi: 10.1002/anie.201501714. Epub 2015 Jun 19.


Microtubules are regulated by microtubule-associated proteins. However, little is known about the structure of microtubule-associated proteins in complex with microtubules. Herein we show that the microtubule-associated protein Tau, which is intrinsically disordered in solution, locally folds into a stable structure upon binding to microtubules. While Tau is highly flexible in solution and adopts a β-sheet structure in amyloid fibrils, in complex with microtubules the conserved hexapeptides at the beginning of the Tau repeats two and three convert into a hairpin conformation. Thus, binding to microtubules stabilizes a unique conformation in Tau.

Keywords: Alzheimer’s disease; NMR spectroscopy; Tau protein; microtubules; structure elucidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / chemistry*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Microtubules / chemistry*
  • Protein Conformation
  • Protein Folding*
  • tau Proteins / chemistry*


  • Amyloid
  • tau Proteins