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Cocrystal structure of a class I preQ1 riboswitch reveals a pseudoknot recognizing an essential hypermodified nucleobase

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Abstract

Riboswitches are mRNA domains that bind metabolites and modulate gene expression in cis. We report cocrystal structures of a remarkably compact riboswitch (34 nucleotides suffice for ligand recognition) from Bacillus subtilis that is selective for the essential nucleobase preQ1 (7-aminomethyl-7-deazaguanine). The structures reveal a previously unrecognized pseudoknot fold and suggest a conserved gene-regulatory mechanism whereby ligand binding promotes sequestration of an RNA segment that otherwise assembles into a transcriptional antiterminator.

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Figure 1: PreQ1 riboswitch structure.
Figure 2: PreQ1 recognition and control of gene expression.

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Acknowledgements

We thank the staff of Advanced Light Source (ALS) beamline 5.0.1 and J. Bolduc for assistance with synchrotron and home laboratory data collection, respectively, R. Huang (University of Illinois at Urbana-Champaign) for his gift of preQ1, and N. Baird, T. Hamma, C. Hoang, N. Kulshina, J. Pitt, J. Posakony, A. Roll-Mecak and H. Xiao for discussions. This work was supported by grants from the Damon Runyon Cancer Research Foundation (DRG-1863-05 to D.J.K. and DRG-1844-04 to T.E.E.), the Howard Hughes Medical Institute (A.R.F.-D.), the US National Institutes of Health (K99 GM084076-01 to D.J.K.) and the W.M. Keck Foundation (A.R.F.-D.).

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  1. Daniel J Klein & Thomas E Edwards

    Present address: Present addresses: Merck Global Structural Biology, Merck & Co., West Point, Pennsylvania 19486, USA (D.J.K.); deCODE Biostructures, 7869 Northeast Day Road West, Bainbridge Island, Washington 98110, USA (T.E.E.).,

Authors and Affiliations

  1. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, 98109-1024, Washington, USA

    Daniel J Klein, Thomas E Edwards & Adrian R Ferré-D'Amaré

  2. Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, 98109-1024, Washington, USA

    Adrian R Ferré-D'Amaré

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  1. Daniel J Klein
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Correspondence to Adrian R Ferré-D'Amaré.

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Supplementary Figures 1–5, Supplementary Tables 1 and 2 and Supplementary Methods (PDF 5258 kb)

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Klein, D., Edwards, T. & Ferré-D'Amaré, A. Cocrystal structure of a class I preQ1 riboswitch reveals a pseudoknot recognizing an essential hypermodified nucleobase. Nat Struct Mol Biol 16, 343–344 (2009). https://doi.org/10.1038/nsmb.1563

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  • DOI: https://doi.org/10.1038/nsmb.1563

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