Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 24, Pages 7501-7506Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1504081112
Keywords
Tau; microtubule; NMR spectroscopy; Alzheimer's disease; chemical cross-linking
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Funding
- Max Planck Gesellschaft consortium Toxic Protein Conformation
- Wellcome Trust
- Deutsche Forschungsgemeinschaft [ZW 71/8-1]
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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.
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