Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 59,633 bioRxiv papers from 265,294 authors.

Atomic model of microtubule-bound tau

By Elizabeth H Kellogg, Nisreen M.A. Hejab, Simon Poepsel, Kenneth H. Downing, Frank DiMaio, Eva Nogales

Posted 16 Feb 2018
bioRxiv DOI: 10.1101/267153 (published DOI: 10.1126/science.aat1780)

Tau is a developmentally regulated protein found in axons, whose physiological role is to stabilize and bundle microtubules (MTs). Hyper-phosphorylation of tau is thought to cause its detachment from MTs and subsequent aggregation into pathological fibrils that have been implicated in Alzheimer's disease pathogenesis. Despite its known MT binding role, there is no consensus regarding which tau residues are crucial for tau-MT interactions, where on the MT tau binds, and how binding results in MT stabilization. We have used cryo-EM to visualize the interaction of different tau constructs with MTs at high resolution (3.2-4.8 Å) and used computational approaches to generate atomic models of tau-tubulin interactions. Our work shows that the highly conserved tubulin-binding repeats within tau adopt very similar structures in their interactions with the MT. Each tau repeat binds the MT exterior and adopts an extended structure along the crest of the protofilament (PF), interacting with both α- and β-tubulin, thus stabilizing the interface between tubulin dimers. Our structures agree with and explain previous biochemical data concerning the effect of phosphorylation on MT affinity and lead to a model in which tau repeats bind in tandem along a PF, tethering together tubulin dimers and stabilizing longitudinal polymerization interfaces. These structural findings could establish a basis of future treatments aiming at the selective stabilization of tau-MT interactions.

Download data

  • Downloaded 1,323 times
  • Download rankings, all-time:
    • Site-wide: 4,250 out of 59,633
    • In molecular biology: 125 out of 1,838
  • Year to date:
    • Site-wide: 29,918 out of 59,633
  • Since beginning of last month:
    • Site-wide: 35,906 out of 59,633

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News