1hht
RNA DEPENDENT RNA POLYMERASE FROM DSRNA BACTERIOPHAGE PHI6 PLUS TEMPLATE
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, resolution 2.9Å | |||||||
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Sites: | , , , , and | ||||||
Ligands: | , , | ||||||
Related: | 1HHS, 1HI0, 1HI1, 1HI8
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Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
Coordinates: | save as pdb, mmCIF, xml |
OverviewOverview
In most RNA viruses, genome replication and transcription are catalysed by a viral RNA-dependent RNA polymerase. Double-stranded RNA viruses perform these operations in a capsid (the polymerase complex), using an enzyme that can read both single- and double-stranded RNA. Structures have been solved for such viral capsids, but they do not resolve the polymerase subunits in any detail. Here we show that the 2 A resolution X-ray structure of the active polymerase subunit from the double-stranded RNA bacteriophage straight phi6 is highly similar to that of the polymerase of hepatitis C virus, providing an evolutionary link between double-stranded RNA viruses and flaviviruses. By crystal soaking and co-crystallization, we determined a number of other structures, including complexes with oligonucleotide and/or nucleoside triphosphates (NTPs), that suggest a mechanism by which the incoming double-stranded RNA is opened up to feed the template through to the active site, while the substrates enter by another route. The template strand initially overshoots, locking into a specificity pocket, and then, in the presence of cognate NTPs, reverses to form the initiation complex; this process engages two NTPs, one of which acts with the carboxy-terminal domain of the protein to prime the reaction. Our results provide a working model for the initiation of replication and transcription.
About this StructureAbout this Structure
1HHT is a Single protein structure of sequence from Pseudomonas phage phi6. Full crystallographic information is available from OCA.
ReferenceReference
A mechanism for initiating RNA-dependent RNA polymerization., Butcher SJ, Grimes JM, Makeyev EV, Bamford DH, Stuart DI, Nature. 2001 Mar 8;410(6825):235-40. PMID:11242087
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