# Molecular structures of tau aggregates studied by solid-state NMR

> **NIH NIH RF1** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $321,779

## Abstract

Project Summary
 Tau is an intrinsically disordered microtubule-associated protein whose misfolding into insoluble
filamentous aggregates is one of the two hallmarks of Alzheimer’s disease. In AD brains the tau
neurofibrillary tangles are hyperphosphorylated, but how phosphorylation converts tau’s functional
structure to its dysfunctional fibril structure is not well understood at the molecular level. We propose to
extend the parent grant by investigating the structural dynamics of a proline-rich region of tau. This
region has been implicated to play a significant role in microtubule binding and is known to contain
many hyperphosphorylation sites of tau. We will study how this proline-rich domain changes its
conformation and dynamics upon binding to microtubules, and how phosphorylation regulates the
binding equilibrium and the conformational equilibrium. We will obtain this information by measuring
solid-state NMR spectra of the proline-rich peptide in the free and bound states without and with
phosphorylation. Molecular insights gained from this study will be integrated into our investigation of the
full-length tau in the parent grant.
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## Key facts

- **NIH application ID:** 10230898
- **Project number:** 3RF1AG059661-01S1
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Mei Hong
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $321,779
- **Award type:** 3
- **Project period:** 2018-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10230898

## Citation

> US National Institutes of Health, RePORTER application 10230898, Molecular structures of tau aggregates studied by solid-state NMR (3RF1AG059661-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10230898. Licensed CC0.

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