title: Folding of the Tau Protein on Microtubules.
abstract: 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.
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany).|Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Göttingen (Germany).|Center for the Molecular Physiology of the Brain, University Medical Center, Göttingen (Germany).
authors.forename: Harindranath
authors.initials: H
authors.lastname: Kadavath
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany).|Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Göttingen (Germany).|Center for the Molecular Physiology of the Brain, University Medical Center, Göttingen (Germany).
authors.forename: Mariusz
authors.initials: M
authors.lastname: Jaremko
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany).|Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Göttingen (Germany).|Center for the Molecular Physiology of the Brain, University Medical Center, Göttingen (Germany).
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Jaremko
authors.affiliation: Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) & CAESAR Research Center, Ludwig-Erhard-Allee 2, Bonn (Germany).
authors.forename: Jacek
authors.initials: J
authors.lastname: Biernat
authors.affiliation: Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) & CAESAR Research Center, Ludwig-Erhard-Allee 2, Bonn (Germany).
authors.forename: Eckhard
authors.initials: E
authors.lastname: Mandelkow
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany). markus.zweckstetter@dzne.de.|Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Göttingen (Germany). markus.zweckstetter@dzne.de.|Center for the Molecular Physiology of the Brain, University Medical Center, Göttingen (Germany). markus.zweckstetter@dzne.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Zweckstetter
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008870:Microtubules / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D016875:tau Proteins / Q000737:chemistry*
chemical_list: D000682:Amyloid; D016875:tau Proteins
keywords: Alzheimer’s disease; NMR spectroscopy; Tau protein; microtubules; structure elucidation