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Structure / Function Analysis of Positive-Strand RNA Virus Replication Complexes


EMSL Project ID
51742

Abstract

SARS-CoV-2, Zika, Dengue, and many other dangerous viruses belong to the positive-strand RNA((+)RNA) viruses. Our group first used cryo-electron tomography (cryo-ET) to reveal the organization of viral RNA and protein components in membrane-bounded (+)RNA virus genome replication complexes. This included discovering a ringed “crown” complex of viral proteins guiding product RNA synthesis and release. A similar complex was just found in coronaviruses, highlighting conservation of RNA replication across (+)RNA viruses. Our recent 8.45 Å structure of the Nodavirus crown revealed that it is composed of 12 copies of multifunctional viral protein A with the viral RNA polymerase domain at the crown apex. We will now extend valuable preliminary results to map RNA capping and other domains in the crown, define dynamic conformational changes in crown assembly and function, and bridge cryo-ET to single particle imaging. The results should have fundamental implications for the function and control of many viruses

Project Details

Start Date
2020-11-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Paul Ahlquist
Institution
University of Wisconsin, Madison

Team Members

Masaki Nishikiori
Institution
University of Wisconsin, Madison

Harry Scott
Institution
Oregon Health & Science University

Janice Pennington
Institution
University of Wisconsin, Madison

Nuruddin Unchwaniwala
Institution
University of Wisconsin, Madison

Hong Zhan
Institution
University of Wisconsin, Madison

Irina El Khoury
Institution
Environmental Molecular Sciences Laboratory