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Bacterial Artificial Chromosomes: A Functional Genomics Tool for the Study of Positive-strand RNA Viruses
Published on: December 29, 2015
RNA-dependent RNA polymerases from Flaviviridae
Kyung H Choi1, Michael G Rossmann
1Department of Biochemistry & Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch at Galveston, TX 77555-0647, USA. kychoi@utmb.edu
Current Opinion in Structural Biology
|November 17, 2009
Summary
Flaviviridae RNA-dependent RNA polymerases (RdRps) have a unique structure enabling de novo RNA synthesis. Conformational changes are crucial for accommodating RNA products during viral genome replication.
Area of Science:
- Virology
- Molecular Biology
- Structural Biology
Background:
- Viral genome replication in Flaviviridae relies on virally encoded RNA-dependent RNA polymerase (RdRp).
- Flaviviridae RdRp utilizes a de novo RNA synthesis mechanism, distinct from the primer-dependent mechanism in Picornaviridae.
Purpose of the Study:
- To elucidate the structural characteristics of Flaviviridae RdRp.
- To understand how RdRp structure facilitates de novo initiation and RNA elongation.
Main Methods:
- Structural analysis of Flaviviridae RdRp.
- Comparison with other viral and cellular polymerases.
Main Results:
- Flaviviridae RdRps possess a right-hand structure with distinctive large thumb domain and C-terminal motif.
- These features create a restricted template-binding channel, favoring single-stranded RNA entry.
- The closed polymerase structure stabilizes de novo initiation complexes.
Conclusions:
- The unique structure of Flaviviridae RdRp is adapted for de novo initiation.
- Significant conformational flexibility is required for accommodating the RNA duplex during elongation.
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