Anti-frameshifting ligand reduces the conformational plasticity of the SARS virus pseudoknot

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DOIResolve DOI: http://doi.org/10.1021/ja410344b
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TypeArticle
Journal titleJournal of the American Chemical Society
ISSN0002-7863
Volume136
Issue6
Pages21962199; # of pages: 4
AbstractProgrammed -1 ribosomal frameshifting (-1 PRF) stimulated by mRNA pseudoknots regulates gene expression in many viruses, making pseudoknots potential targets for anti-viral drugs. The mechanism by which pseudoknots trigger -1 PRF, however, remains controversial, with several competing models. Recent work showed that high -1 PRF efficiency was linked to high pseudoknot conformational plasticity via the formation of alternate conformers. We tested whether pseudoknots bound with an anti-frameshifting ligand exhibited a similar correlation between conformational plasticity and -1 PRF efficiency by measuring the effects of a ligand that was found to inhibit -1 PRF in the SARS coronavirus on the conformational dynamics of the SARS pseudoknot. Using single-molecule force spectroscopy to unfold pseudoknots mechanically, we found that the ligand binding effectively abolished the formation of alternate conformers. This result extends the connection between -1 PRF and conformational dynamics and, moreover, suggests that targeting the conformational dynamics of pseudoknots may be an effective strategy for anti-viral drug design. © 2014 American Chemical Society.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); National Institute for Nanotechnology (NINT-INNT)
Peer reviewedYes
NPARC number21272224
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Record identifiera92c3708-2240-4b0f-89e9-573ecb2a0b6c
Record created2014-07-23
Record modified2016-05-09
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