Picornaviral loop-to-loop replication complex.

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dc.contributor.authorClaridge, JKen_AU
dc.contributor.authorHeadey, SJen_AU
dc.contributor.authorChow, JYHen_AU
dc.contributor.authorSchwalbe, Men_AU
dc.contributor.authorEdwards, PJen_AU
dc.contributor.authorJeffries, CMen_AU
dc.contributor.authorVenugopal, Hen_AU
dc.contributor.authorTrewhella, Jen_AU
dc.contributor.authorPascal, SMen_AU
dc.date.accessioned2009-06-16T04:08:42Zen_AU
dc.date.accessioned2010-04-30T05:03:59Zen_AU
dc.date.available2009-06-16T04:08:42Zen_AU
dc.date.available2010-04-30T05:03:59Zen_AU
dc.date.issued2009-06en_AU
dc.date.statistics2009-06en_AU
dc.description.abstractPicornaviruses replicate their RNA genomes through a highly conserved mechanism that involves an interaction between the principal viral protease (3C(pro)) and the 5'-UTR region of the viral genome. The 3C(pro) catalytic site is the target of numerous replication inhibitors. This paper describes the first structural model of a complex between a picornaviral 3C(pro) and a region of the 5'-UTR, stem-loop D (SLD). Using human rhinovirus as a model system, we have combined NMR contact information, small-angle X-ray scattering (SAXS) data, and previous mutagenesis results to determine the shape, position and relative orientation of the 3C(pro) and SLD components. The results clearly identify a 1:1 binding stoichiometry, with pronounced loops from each molecule providing the key binding determinants for the interaction. Binding between SLD and 3C(pro) induces structural changes in the proteolytic active site that is positioned on the opposite side of the protease relative to the RNA/protein interface, suggesting that subtle conformational changes affecting catalytic activity are relayed through the protein. © 2009, Elsevier Ltd.en_AU
dc.identifier.citationClaridge, J. K., Headey, S. J., Chow, J. Y. H., Schwalbe, M., Edwards, P. J., Jeffries, C. M., Venugopal, H., Trewhella, J., & Pascal, S. M. (2009). A picornaviral loop-to-loop replication complex. Journal of Structural Biology, 166(3), 251-262. doi:10.1016/j.jsb.2009.02.010en_AU
dc.identifier.govdoc1261en_AU
dc.identifier.issn1047-8477en_AU
dc.identifier.issue3en_AU
dc.identifier.journaltitleJournal of Structural Biologyen_AU
dc.identifier.pagination251-262en_AU
dc.identifier.urihttp://dx.doi.org/10.1016/j.jsb.2009.02.010en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/1374en_AU
dc.identifier.volume166en_AU
dc.language.isoenen_AU
dc.publisherElsevieren_AU
dc.subjectNuclear magnetic resonanceen_AU
dc.subjectSmall angle scatteringen_AU
dc.subjectGenome mutationsen_AU
dc.subjectProteinsen_AU
dc.subjectDNA replicationen_AU
dc.subjectMutagenesisen_AU
dc.titlePicornaviral loop-to-loop replication complex.en_AU
dc.typeJournal Articleen_AU
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