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Structure of Hepatitis C Virus Polymerase in Complex with Primer- Template RNA.
- Source :
-
Journal of Virology . Jun2012, Vol. 86 Issue 12, p6503-6511. 9p. - Publication Year :
- 2012
-
Abstract
- The replication of the hepatitis C viral (HCV) genome is accomplished by the NS5B RNA-dependent RNA polymerase (RdRp), for which mechanistic understanding and structure-guided drug design efforts have been hampered by its propensity to crystallize in a closed, polymerization-incompetent state. The removal of an autoinhibitory ß-hairpin loop from genotype 2a HCV NS5B increases de novo RNA synthesis by > 100-fold, promotes RNA binding, and facilitated the determination of the first crystallographic structures of HCV polymerase in complex with RNA primer-template pairs. These crystal structures demonstrate the structural realignment required for primer-template recognition and elongation, provide new insights into HCV RNA synthesis at the molecular level, and may prove useful in the structure-based design of novel antiviral compounds. Additionally, our approach for obtaining the RNA primer-template-bound structure of HCV polymerase may be generally applicable to solving RNA-bound complexes for other viral RdRps that contain similar regulatory ß-hairpin loops, including bovine viral diarrhea virus, dengue virus, and West Nile virus. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0022538X
- Volume :
- 86
- Issue :
- 12
- Database :
- Academic Search Index
- Journal :
- Journal of Virology
- Publication Type :
- Academic Journal
- Accession number :
- 77817698
- Full Text :
- https://doi.org/10.1128/JVI.00386-12