New strategies for visualizing a powerful molecular motor
Abstract
Core biological processes are driven by proteins and nucleic acids working together to fulfill the instructions of our genetic code. Many dynamic and essential processes are driven by multicomponent biomolecular complexes. While many widely used structural biology approaches are useful to understand how molecular machines function in isolation, the next advance in our understanding will come when we are able to visualize how these machines function in a cellular context - within real cells. Here, we propose to use recent advances in data processing and data collection to reveal native structures at unprecedented resolution. We seek to understand the mechanism of viral genome packaging in herpesviruses, ubiquitous human pathogens that cause a variety of disease. To protect their double-stranded DNA genome, condense it into a small volume, and transport it to a new host, herpesviruses must actively package their genome into a pre-formed capsid. A powerful viral motor is responsible for packaging. Here, we propose to (1) determine the structure of an actively packaging motor in vitro, using purified components and single-particle cryo-EM analysis, and (2) capture an actively packaging motor during viral replication using an innovative FIB-milling cryo-EM-cryo-ET approach. Our long term goal is to define every step of the herpesvirus lifecycle through high-resolution imaging.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Feb 06, 2025
- Source ID
- FA95502410238
Entities
People
- Allison Didychuk
Organizations
- Air Force Office of Scientific Research
- United States Air Force
- Yale University