title: Tau stabilizes microtubules by binding at the interface between tubulin heterodimers.
abstract: The structure, dynamic behavior, and spatial organization of microtubules are regulated by microtubule-associated proteins. An important microtubule-associated protein is the protein Tau, because its microtubule interaction is impaired in the course of Alzheimer's disease and several other neurodegenerative diseases. Here, we show that Tau binds to microtubules by using small groups of evolutionary conserved residues. The binding sites are formed by residues that are essential for the pathological aggregation of Tau, suggesting competition between physiological interaction and pathogenic misfolding. Tau residues in between the microtubule-binding sites remain flexible when Tau is bound to microtubules in agreement with a highly dynamic nature of the Tau-microtubule interaction. By binding at the interface between tubulin heterodimers, Tau uses a conserved mechanism of microtubule polymerization and, thus, regulation of axonal stability and cell morphology.
authors.affiliation: Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany;
authors.forename: Harindranath
authors.initials: H
authors.lastname: Kadavath
authors.affiliation: Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany;
authors.forename: Romina V
authors.initials: RV
authors.lastname: Hofele
authors.affiliation: Deutsches Zentrum für Neurodegenerative Erkrankungen, Ludwig-Erhard-Allee 2, Bonn, Germany;
authors.forename: Jacek
authors.initials: J
authors.lastname: Biernat
authors.affiliation: Deutsches Zentrum für Neurodegenerative Erkrankungen, Ludwig-Erhard-Allee 2, Bonn, Germany;
authors.forename: Satish
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Deutsches Zentrum für Neurodegenerative Erkrankungen, Ludwig-Erhard-Allee 2, Bonn, Germany;
authors.forename: Katharina
authors.initials: K
authors.lastname: Tepper
authors.affiliation: Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany; Bioanalytics, Department of Clinical Chemistry, University Medical Center, 37075 Göttingen, Germany;
authors.forename: Henning
authors.initials: H
authors.lastname: Urlaub
authors.affiliation: Deutsches Zentrum für Neurodegenerative Erkrankungen, Ludwig-Erhard-Allee 2, Bonn, Germany; 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, 37077 Göttingen, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen, 37077 Göttingen, Germany; Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center, 37075 Göttingen, Germany markus.zweckstetter@dzne.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Zweckstetter
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D055592:Biophysical Phenomena; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D013552:Swine; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism*; D014747:Vinblastine / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C054369:MAPT protein, human; D020033:Protein Isoforms; D014404:Tubulin; D016875:tau Proteins; D014747:Vinblastine
keywords: Alzheimer's disease; NMR spectroscopy; Tau; chemical cross-linking; microtubule