Three conformational snapshots of the hepatitis C virus NS3 helicase reveal a ratchet translocation mechanism.

ABSTRACT: A virally encoded superfamily-2 (SF2) helicase (NS3h) is essential for the replication of hepatitis C virus, a leading cause of liver disease worldwide. Efforts to elucidate the function of NS3h and to develop inhibitors against it, however, have been hampered by limited understanding of its molecular mechanism. Here we show x-ray crystal structures for a set of NS3h complexes, including ground-state and transition-state ternary complexes captured with ATP mimics (ADP.BeF(3) and ). These structures provide, for the first time, three conformational snapshots demonstrating the molecular basis of action for a SF2 helicase. Upon nucleotide binding, overall domain rotation along with structural transitions in motif V and the bound DNA leads to the release of one base from the substrate base-sta

SUBMITTER: Gu M 

PROVIDER: S-EPMC2818896 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature