Tau Binds to Multiple Tubulin Dimers with Helical Structure

Area of Science:

• Biochemistry and Molecular Biology
• Neuroscience
• Structural Biology

Background:

• Tau protein's native function in microtubule (MT) assembly is critical, and its dysfunction is implicated in neurodegenerative diseases.
• Studying tau's mechanism is challenging due to its intrinsic disorder and dynamic nature.

Purpose of the Study:

• To investigate the stoichiometry and structural characteristics of tau-tubulin assemblies.
• To understand how tau interacts with tubulin and potentially contributes to MT assembly.

Main Methods:

• Utilized fluorescence correlation spectroscopy (FCS).
• Employed acrylodan fluorescence screening.
• Studied tau-tubulin complexes under conditions inhibiting MT assembly.

Main Results:

• Tau binds to multiple tubulin dimers, irrespective of MT assembly inhibition.
• Observed helical structure in the MT-binding domain of tau within tau-tubulin complexes, indicating partial folding.
• Demonstrated a disorder-to-order transition in tau upon tubulin binding.

Conclusions:

• Tau's intrinsic disorder acts as a flexible scaffold for tubulin and MT binding.
• The disorder-to-order transition is a key mechanism mediating tau-tubulin interactions.
• Findings provide a mechanistic basis for tau's role in MT dynamics and neurodegeneration.