In:
Journal of Virology, American Society for Microbiology, Vol. 86, No. 12 ( 2012-06-15), p. 6503-6511
Kurzfassung:
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 β-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 β-hairpin loops, including bovine viral diarrhea virus, dengue virus, and West Nile virus.
Materialart:
Online-Ressource
ISSN:
0022-538X
,
1098-5514
DOI:
10.1128/JVI.00386-12
Sprache:
Englisch
Verlag:
American Society for Microbiology
Publikationsdatum:
2012
ZDB Id:
1495529-5
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