1hi0: Difference between revisions
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==Overview== | ==Overview== | ||
In most RNA viruses, genome replication and transcription are catalysed by | 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 Structure== | ==About this Structure== | ||
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[[Category: Bacteriophage phi-6]] | [[Category: Bacteriophage phi-6]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bamford, D | [[Category: Bamford, D H.]] | ||
[[Category: Butcher, S | [[Category: Butcher, S J.]] | ||
[[Category: Grimes, J | [[Category: Grimes, J M.]] | ||
[[Category: Makeyev, E | [[Category: Makeyev, E V.]] | ||
[[Category: Stuart, D | [[Category: Stuart, D I.]] | ||
[[Category: GTP]] | [[Category: GTP]] | ||
[[Category: MG]] | [[Category: MG]] | ||
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[[Category: viral polymerase]] | [[Category: viral polymerase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:01:26 2008'' | ||
Revision as of 14:01, 21 February 2008
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RNA DEPENDENT RNA POLYMERASE FROM DSRNA BACTERIOPHAGE PHI6 PLUS INITIATION COMPLEX
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
1HI0 is a Single protein structure of sequence from Bacteriophage phi-6 with , and as ligands. Known structural/functional Sites: , , , , , , , and . 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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