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Title: Recognition of the bacterial alarmone ZMP through long-distance association of two RNA subdomains

Journal Article · · Nature Structural & Molecular Biology
DOI:https://doi.org/10.1038/nsmb.3073· OSTI ID:1222002
 [1];  [1]
  1. National Inst. of Health (NIH), Bethesda, MD (United States). National Heart, Lung, and Blood Inst. Biochemistry and Biophysics Center

The bacterial alarmone 5-aminoimidazole-4-carboxamide riboside 5'-triphosphate (AICAR triphosphate or ZTP), derived from the monophosphorylated purine precursor ZMP, accumulates during folate starvation. ZTP regulates genes involved in purine and folate metabolism through a cognate riboswitch. The linker connecting this riboswitch's two subdomains varies in length by over 100 nucleotides. In this paper, we report the cocrystal structure of the Fusobacterium ulcerans riboswitch bound to ZMP, which spans the two subdomains whose interface also comprises a pseudoknot and ribose zipper. The riboswitch recognizes the carboxamide oxygen of ZMP through an unprecedented inner-sphere coordination with a Mg2+ ion. We show that the affinity of the riboswitch for ZMP is modulated by the linker length. Notably, ZMP can simultaneously bind to the two subdomains even when they are synthesized as separate RNAs. Finally, the ZTP riboswitch demonstrates how specific small-molecule binding can drive association of distant noncoding-RNA domains to regulate gene expression.

Research Organization:
National Institutes of Health (NIH), Bethesda, MD (United States)
Sponsoring Organization:
USDOE; National Inst. of Health (NIH) (United States)
OSTI ID:
1222002
Journal Information:
Nature Structural & Molecular Biology, Vol. 22, Issue 9; ISSN 1545-9993
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 28 works
Citation information provided by
Web of Science

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Cited By (9)

Synthetic ligands for PreQ1 riboswitches provide structural and mechanistic insights into targeting RNA tertiary structure journal April 2019
A ligand-gated strand displacement mechanism for ZTP riboswitch transcription control journal October 2019
A mechanism for ligand gated strand displacement in ZTP riboswitch transcription regulation preprint February 2019
Co-crystal structure of the Fusobacterium ulcerans ZTP riboswitch using an X-ray free-electron laser journal June 2019
The ancient alarmone ZTP and zinc homeostasis in Bacillus subtilis journal July 2019
Riboswitch diversity and distribution journal April 2017
Evolutionary convergence in the biosyntheses of the imidazole moieties of histidine and purines journal April 2018
Co-crystal structure of the Fusobacterium ulcerans ZTP riboswitch using an X-ray free-electron laser text January 2019
Mechanistic Insights into Cofactor-Dependent Coupling of RNA Folding and mRNA Transcription/Translation by a Cobalamin Riboswitch journal May 2016

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