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Generation and Assembly of Virus-Specific Nucleocapsids of the Respiratory Syncytial Virus
Published on: July 27, 2021
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Structural insights into reptarenavirus cap-snatching machinery
Maria Rosenthal1, Nadja Gogrefe1, Dominik Vogel1
1Department of Virology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany.
Plos Pathogens
|May 16, 2017
Summary
Researchers found a functional cap-snatching endonuclease in reptarenavirus L protein but a degenerate cap-binding domain, suggesting evolutionary links and altered mechanisms in arenaviruses.
Area of Science:
- Virology
- Structural Biology
- Molecular Evolution
Background:
- Cap-snatching is a viral RNA synthesis mechanism crucial for influenza viruses.
- Endonuclease and cap-binding domains in influenza virus polymerase are well-characterized.
- Cap-snatching endonucleases exist in various virus families, but cap-binding domains remain elusive in some.
Purpose of the Study:
- To investigate the structure and function of the L protein from California Academy of Sciences virus (CASV), a reptarenavirus.
- To elucidate the evolutionary relationship between reptarenavirus and other virus polymerases involved in cap-snatching.
- To determine the presence and nature of cap-binding and endonuclease activities in the CASV L protein.
Main Methods:
- X-ray crystallography was employed to solve the structures of the C-terminal (L-Cterm) and N-terminal endonuclease domains of the CASV L protein.
- Structural comparisons were made between CASV L protein domains and known influenza virus polymerase domains.
- Biochemical assays were performed to assess cap-binding activity of the CASV L-Cterm fragment.
Main Results:
- The CASV L-Cterm structure revealed domains homologous to influenza virus cap-binding and adjacent domains, despite lacking sequence similarity, suggesting common ancestry.
- A potential cap-binding site was identified in CASV L-Cterm, but biochemical assays failed to detect cap-binding, indicating a degenerate domain.
- The N-terminal endonuclease domain of CASV L protein exhibited a typical fold and active site configuration, similar to known mammarenavirus endonucleases.
Conclusions:
- Reptarenaviruses possess a functional cap-snatching endonuclease in their L protein N-terminus and a degenerate cap-binding domain in the C-terminus.
- Structural similarities suggest a shared evolutionary origin for cap-snatching machinery across different virus families.
- The findings imply potential variations in the cap-snatching mechanism within the arenavirus family.
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