Читать книгу Principles of Virology - Jane Flint, S. Jane Flint - Страница 279

Base-paired regions in viral RNA must be disrupted to permit copying by RdRP. RNA helicases, which are encoded in the genomes of many RNA viruses, are thought to unwind the genomes of double-stranded RNA viruses, as well as secondary structures in template RNAs. They also prevent extensive base pairing between template RNA and the nascent complementary strand. The RNA helicases of several viruses that are important human pathogens, including the flaviviruses hepatitis C virus and dengue virus, have been studied extensively because they are potential targets for therapeutic intervention. To facilitate the development of new agents that inhibit these helicases, their three-dimensional structures have been determined by X-ray crystallography. These molecules comprise three domains that mediate hydrolysis of NTPs and RNA binding (Fig. 6.15). Between the domains is a cleft that is large enough to accommodate single-stranded but not double-stranded RNA. Unwinding of double-stranded RNA probably occurs as one strand of RNA passes through the cleft and the other is excluded.

The bacteriophage ϕ6 RNA polymerase can separate the strands of double-stranded RNA without the activity of a helicase. Examination of the structure of the enzyme suggests how such melting might be accomplished. This RdRP has a plow-like protuberance around the entrance to the template channel that is thought to separate the two strands, allowing only one to enter the channel.