# Structure and Function of Essential Nucleoprotein Complexes Along a Viral Genome Packaging Pathway

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2024 · $66,362

## Abstract

Project Summary/Abstract:
A key step in the assembly of the large double-stranded DNA (dsDNA) viruses is packaging of a genome into a
pre-assembled procapsid by an ATP-driven motor complex. In the herpesviruses and many bacteriophages,
packaging is catalyzed by a terminase enzyme that utilizes a concatemeric genome substrate. To accomplish
this, terminase enzymes assemble into distinct initiation, motor and termination complexes to processively excise
an individual genome from the concatemer, and concomitantly package it into the capsid. This requires that the
enzymes cycle between stable nuclease and dynamic motor intermediates. While our understanding of
packaging initiation and motor translocation is extensive, termination of genome packaging remains ill-studied
and poorly characterized in all viruses, primarily because defined experimental systems have not been
developed. Phage  is an exception wherein rigorous biochemical assays allow molecular dissection of the
entire assembly pathway. This multi-PI application proposes to use phage  to interrogate termination, the final
and most poorly characterized step in the packaging pathway. Two fundamental questions central to genome
packaging are addressed; (i) how does the translocating motor recognize the genome end while also sensing
that a sufficient length of DNA has been packaged, transition to a site-specifically bound nuclease complex, and
(ii) how do “finishing proteins” promote end maturation and terminase ejection from the nucleocapsid without
loss of the tightly packaged DNA. We describe highly integrated and synergistic biochemical, biophysical, single-
molecule and structural approaches to characterize this conserved and essential, yet largely unstudied step in
virus assembly. Given that this process is strongly conserved in all of the dsDNA viruses, both prokaryotic and
eukaryotic, and the commonality of initiation-translocation-termination pathways in biology, the results will have
broad implications in virology and cell biology.

## Key facts

- **NIH application ID:** 10987559
- **Project number:** 3R01GM127365-06S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Carlos Enrique Catalano
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $66,362
- **Award type:** 3
- **Project period:** 2018-05-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10987559

## Citation

> US National Institutes of Health, RePORTER application 10987559, Structure and Function of Essential Nucleoprotein Complexes Along a Viral Genome Packaging Pathway (3R01GM127365-06S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10987559. Licensed CC0.

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