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Proc Natl Acad Sci U S A. 2015 Jun 16;112(24):7501-6. doi: 10.1073/pnas.1504081112. Epub 2015 Jun 1.

Tau stabilizes microtubules by binding at the interface between tubulin heterodimers.

Author information

1
Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany;
2
Deutsches Zentrum für Neurodegenerative Erkrankungen, Ludwig-Erhard-Allee 2, Bonn, Germany;
3
Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany; Bioanalytics, Department of Clinical Chemistry, University Medical Center, 37075 Göttingen, Germany;
4
Deutsches Zentrum für Neurodegenerative Erkrankungen, Ludwig-Erhard-Allee 2, Bonn, Germany; CAESAR Research Center, Ludwig-Erhard-Allee 2, Bonn, Germany;
5
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.

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.

KEYWORDS:

Alzheimer's disease; NMR spectroscopy; Tau; chemical cross-linking; microtubule

PMID:
26034266
PMCID:
PMC4475932
DOI:
10.1073/pnas.1504081112
[Indexed for MEDLINE]
Free PMC Article

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