Structural polymorphism of 441-residue Tau at single residue resolution
2009

Understanding the Structure of Tau Protein in Alzheimer's Disease

publication Evidence: high

Author Information

Author(s): Mukrasch Marco D, Bibow Stefan, Korukottu Jegannath, Jeganathan Sadasivam, Biernat Jacek, Griesinger Christian, Mandelkow Eckhard, Zweckstetter Markus

Primary Institution: Max Planck Institute for Biophysical Chemistry, Göttingen, Germany

Hypothesis

Can nuclear magnetic resonance (NMR) spectroscopy provide detailed insights into the structural polymorphism of the tau protein?

Conclusion

NMR spectroscopy reveals that the tau protein is highly dynamic in solution and has an intricate network of transient long-range contacts important for its aggregation.

Supporting Evidence

  • NMR spectroscopy can provide detailed insight into the structural polymorphism of very large nonglobular proteins.
  • The study reveals that 441-residue tau is highly dynamic in solution.
  • Unique insights into the interaction of tau with microtubules were obtained through single-residue NMR analysis.
  • The findings suggest that tau's structural properties are crucial for its function and aggregation in Alzheimer's disease.

Takeaway

The tau protein, which is important in Alzheimer's disease, can change shape a lot, and scientists used a special technique to see how it moves and interacts with other parts of the cell.

Methodology

The study used nuclear magnetic resonance (NMR) spectroscopy to analyze the structure and dynamics of the tau protein at single residue resolution.

Limitations

The study's findings may be limited by the inherent challenges of studying large, natively unfolded proteins using NMR.

Digital Object Identifier (DOI)

10.1371/journal.pbio.1000034

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