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Title: Picornaviral loop-to-loop replication complex.
Authors: Claridge, JK
Headey, SJ
Chow, JYH
Schwalbe, M
Edwards, PJ
Jeffries, CM
Venugopal, H
Trewhella, J
Pascal, SM
Keywords: Nuclear magnetic resonance
Small angle scattering
Genome mutations
DNA replication
Issue Date: Jun-2009
Publisher: Elsevier
Citation: Claridge, 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.2009.02.010
Abstract: Picornaviruses 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.
Gov't Doc #: 1261
ISSN: 1047-8477
Appears in Collections:Journal Articles

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