Near-atomic model of microtubule-tau interactions

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• Tau is an axonal protein essential for stabilizing microtubules (MTs).
• Hyperphosphorylated tau detaches from MTs, aggregates, and is implicated in Alzheimer's disease.
• The precise mechanisms of tau-MT interaction and stabilization remain unclear.

Purpose of the Study:

• To elucidate the atomic details of tau-tubulin interactions.
• To understand how tau stabilizes microtubules.
• To investigate the impact of phosphorylation on tau's MT binding affinity.

Main Methods:

• Cryo-electron microscopy (cryo-EM) of tau constructs on microtubules.
• Computational modeling to generate atomic models of tau-tubulin interactions.

Main Results:

• Tau's conserved tubulin-binding repeats adopt extended structures along protofilament crests.
• These structures stabilize the interface between tubulin dimers.
• A model of tandem repeat binding along protofilaments was proposed, tethering tubulin dimers and stabilizing MT polymerization.

Conclusions:

• The study provides atomic-level insights into tau-MT interactions.
• The findings explain how tau phosphorylation affects MT binding.
• The proposed model clarifies tau's role in microtubule stabilization.