# Multisubunit viral ATPases that couple ATP-hydrolysis to genome translocation

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2020 · $327,600

## Abstract

Project Summary
Viral genome packaging is a complex, non-spontaneous, multi-step enzymatic reaction that in tailed
bacteriophages and herpesviruses proceeds via formation of an empty precursor capsid (or procapsid) that is
filled with genetic material by the action of two proteins, known as large and small terminase. Though
commonly studied as individual subunits, viral terminases bind, pump and cleave viral DNA assembled into
large macromolecular complexes of poorly characterized structure, function and composition. The recent
discovery of a potent antiviral agent specific to Human Cytomegalovirus small terminase subunit (pUL56) has
grown further interest in viral packaging motors.
In this grant, combining hybrid methods in structural biology (i.e. X-crystallography, cryo-electron microscopy,
hydrogen/deuterium exchange mass spectrometry) with modern biochemical approaches (i.e. conformation-
specific synthetic Fabs, site directed mutagenesis, yeast 1-hybrid), we seek to understand the principles
governing viral genome packaging through the comparative analysis of motors from different DNA viruses. We
are particularly interested in deciphering the atomic structure of macromolecular assemblies formed by
terminase subunits during the packaging reaction and the role of S-terminase that is functionally conserved
from bacterial viruses to herpesviruses. This research tries to fill a significant and growing knowledge gap
between the enzymology of genome packaging, which is increasing well-understood thanks to single molecule
biophysical studies, and the molecular machines catalyzing packaging. Building upon the work initiated in the
previous funding cycle, we seek to: 1.) Elucidate the architecture of terminase assemblies formed during viral
genome packaging; 2.) Determine the conserved architecture of Human Cytomegalovirus small terminase
(pUL56) and its interaction with viral DNA and the antiviral drug letermovir.

## Key facts

- **NIH application ID:** 9988416
- **Project number:** 5R01GM100888-08
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Gino Cingolani
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $327,600
- **Award type:** 5
- **Project period:** 2012-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988416

## Citation

> US National Institutes of Health, RePORTER application 9988416, Multisubunit viral ATPases that couple ATP-hydrolysis to genome translocation (5R01GM100888-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9988416. Licensed CC0.

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