# Magnetic resonance spectroscopy (Binyong Liang)

> **NIH NIH P01** · UNIVERSITY OF VIRGINIA · 2020 · $106,803

## Abstract

PROJECT SUMMARY 
The overall goal of this program project is to elucidate the precise molecular mechanism and regulation of the 
fusion machine that drives exocytosis for the controlled release of neurotransmitter at nerve terminals. The 
assembly of SNARE molecules residing in the synaptic vesicle and presynaptic plasma membrane takes 
center stage and provides the driving energy for this process. Even though we know the structure of the fully 
assembled cis-SNARE complex after fusion in atomic detail and have detailed conformational models for 
several of the SNAREs before fusion, we do not precisely know how (i) they are conditioned with regulatory 
proteins such as Munc18 and Munc13 to form an active acceptor complex on the plasma membrane, (ii) how 
this acceptor SNARE complex engages with the synaptic vesicle SNARE upon encounter, and (iii) how this 
high-energy trans-SNARE complex is ultimately triggered by the synaptic vesicle protein synaptotagmin and 
calcium to proceed to full assembly and fusion. 
Three projects led by three expert leaders in the biochemistry, structural biology, and biophysics of neuronal 
exocytotic membrane fusion are designed to jointly unravel the precise molecular interactions that drive the 
neuronal fusion machine through the vesicle docking, priming, and fusion steps with the highest possible 
structural and time resolution. The team will seek to define the structures and configurations of the active 
presynaptic acceptor SNARE complex and the fusion-restricted trans-SNARE complex between two 
membranes, and the team will strive to uncover the molecular mechanism, by which calcium-synaptotagmin 
engages with the membranes and/or complex to release their fusion-restriction. 
To achieve this goal the team will use a unique combination of approaches ranging from highly innovative 
biochemical procedures to reconstitute the relevant proteins, EPR, DEER, and NMR spectroscopy to 
characterize the pertinent structures in membrane environments, and FLIC and single vesicle TIRF microscopy 
to measure membrane topology and read out fusion on the millisecond timescale.

## Key facts

- **NIH application ID:** 9987653
- **Project number:** 5P01GM072694-14
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** DAVID S CAFISO
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $106,803
- **Award type:** 5
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987653

## Citation

> US National Institutes of Health, RePORTER application 9987653, Magnetic resonance spectroscopy (Binyong Liang) (5P01GM072694-14). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9987653. Licensed CC0.

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