Structural Characterization of Tau in Fuzzy Tau:Tubulin Complexes

Ho Yee Joyce Fung, Kristen M. McKibben, Jennifer Ramirez, Kushol Gupta, Elizabeth Rhoades

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Tau is a neuronal microtubule (MT)-associated protein of significant interest due to its association with several neurodegenerative disorders. Tau's intrinsic disorder and the dynamic nature of its interactions with tubulin and MTs make its structural characterization challenging. Here, we use an environmentally sensitive fluorophore as a site-specific probe of tau bound to soluble tubulin. Comparison of our results with a recently published tau:MT cryoelectron microscopy model reveals structural similarities between tubulin- and MT-bound tau. Analysis of residues across the repeat regions reveals a hierarchy in tubulin occupancy, which may be relevant to tau's ability to differentiate between tubulin and MTs. As binding to soluble tubulin is a critical first step in MT polymerization, our characterization of the structural features of tau in dynamic, fuzzy tau:tubulin assemblies advances our understanding of how tau functions in the cell and how function may be disrupted in disease. Tau and soluble tubulin form highly heterogeneous complexes that stymie structural characterization. Fung et al. use site-specific fluorescence in combination with a published cryo-EM model of microtubule-bound tau to probe structural feature of tau bound to soluble tubulin, which revealed several insights that may inform tau function.

Original languageEnglish (US)
Pages (from-to)378-384.e4
Issue number3
StatePublished - Mar 3 2020
Externally publishedYes


  • acrylodan
  • fluorescence correlation spectroscopy
  • intrinsically disordered protein
  • microtubule
  • tau
  • tubulin

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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