Tau has a native function in the stabilization of neuronal microtubules (MT). It also plays a pathological role in neurodegenerative diseases such as Alzheimer’s. The mechanism of tau’s loss of function from its native to diseased state is not well understood. Tau is an intrinsically disordered protein, which has presented difficulties in studying its structure and function. Here we use acrylodan, an environmentally sensitive fluorescent probe, to observe residue-specific shifts in emission fluorophore as a site-specific probe of tau bound to soluble tubulin. Comparison of our results with a recently published tau:MT cryo-EM model reveals structural similarities between tubulin and MT-bound tau. Analysis of residues across the repeat regions reveal a hierarchy in tubulin binding interactions, 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.

Structural characterization of tau in fuzzy tau:tubulin complexes

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.