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Tau stabilizes microtubules by binding at the interface between tubulin heterodimers

2015; National Academy of Sciences; Volume: 112; Issue: 24 Linguagem: Inglês

10.1073/pnas.1504081112

1091-6490

Harindranath Kadavath, Romina Hofele, Jacek Biernat, Satish Kumar, Katharina Tepper, Henning Urlaub, Eckhard Mandelkow�, Markus Zweckstetter,

14-3-3 protein interactions

Significance Tau is an important microtubule-associated protein. Although the structure–function relationship of Tau has been intensively studied for many years primarily by molecular biology and biochemical approaches, little is still known about the molecular mechanisms by which Tau interacts with microtubules and promotes microtubule assembly. Here, we provide detailed insight into the Tau–microtubule association by using NMR spectroscopy and mass spectrometry. We show that Tau binds to microtubules by using small groups of residues, which are important for pathological aggregation of Tau. We further show that Tau stabilizes a straight protofilament conformation by binding to a hydrophobic pocket in between tubulin heterodimers. Our work is thus relevant to normal Tau action development and in Tau-related neurodegenerative diseases.