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Updated: Apr 22, 2026
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Nuclear Magnetic Resonance Spectroscopy for the Identification of Multiple Phosphorylations of Intrinsically Disordered Proteins
Published on: December 27, 2016
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Simultaneous Profiling and Quantification of Tau and Its Phosphorylated Isomers Using Engineered FraC Nanopores
1Department of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China.
Nano Letters
|April 20, 2026
Summary
This study presents a novel nanopore method for analyzing Tau protein and its phosphorylation in Alzheimer's disease (AD). The technique accurately identifies and quantifies Tau peptides, offering a new diagnostic tool.
Area of Science:
- Biochemistry
- Nanotechnology
- Neuroscience
Background:
- Tau aggregation and hyperphosphorylation are key hallmarks and biomarkers of Alzheimer's disease (AD).
- Simultaneous profiling and quantitative analysis of Tau and its phosphorylated isoforms are technically challenging.
- Current methods struggle with high-resolution characterization of post-translational modifications (PTMs).
Purpose of the Study:
- To develop a high-resolution nanopore-based workflow for real-time identification and quantification of Tau peptides.
- To enable precise resolution and quantification of positional phosphorylation isomers of Tau.
- To advance global analysis of phosphorylated Tau for AD diagnostics.
Main Methods:
- Engineered a high-resolution FraC nanopore (FraCG6DG13F) with enhanced temporal resolution.
- Integrated nanopore detection with machine-learning algorithms for data analysis.
- Applied the workflow to native Tau (2N4R) protein and mixed digestion samples.
Main Results:
- Real-time identification of 12 tryptic peptides from Tau (2N4R) with >91.1% accuracy.
- Precise resolution and quantification of positional phosphorylation isomers at S400 or S402 of Tau.
- Achieved classification accuracy >93% with sensitivity comparable to mass spectrometry.
Conclusions:
- Demonstrated a promising advancement in nanopore-based global analysis of phosphorylated Tau.
- Highlighted the potential of this method for high-resolution characterization and accurate quantification of proteins with PTMs.
- Offers a novel approach for Alzheimer's disease biomarker research.
