The structure of the Guanidine-III Riboswitch

Lin Huang, Jia Wang, Timothy J. Wilson, David M. J. Lilley (Lead / Corresponding author)

Research output: Contribution to journalArticle

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Abstract

We have determined high resolution crystal structures of the ykkC guanidine III riboswitch from Thermobifida fusca. The riboswitch forms a classic H-type pseudoknot, in which a connecting strand locates in the major groove of one duplex to form a triple helix. This is continuous with a central core of conserved nucleotides forming a left handed helical ramp of internucleotide interactions that generates the guanidinium cation binding site. The ligand is hydrogen bonded to O6 and N7 of two guanine nucleobases, and to the 2'OH of a cytidine, the nucleobase of which stacks with the guanidinium in a π-cation interaction. The binding pocket has a side opening through which a small side chain can pass, and we have determined structures with bound methylguanidine, aminoguanidine, ethylguanidine and agmatine. Comparison of this structure with those of the guanidine I and II riboswitches reveals common aspects and contrasts.
Original languageEnglish
Pages (from-to)1407-1415.e2
Number of pages12
JournalCell Chemical Biology
Volume24
Issue number11
Early online date5 Oct 2017
DOIs
Publication statusPublished - 16 Nov 2017

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Riboswitch
Guanidine
Cations
Methylguanidine
Agmatine
Cytidine
Architectural Accessibility
Guanine
Hydrogen
Nucleotides
Crystal structure
Binding Sites
Ligands

Keywords

  • Gene regulation
  • RNA structure
  • X-ray crystallography
  • riboregulation

Cite this

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title = "The structure of the Guanidine-III Riboswitch",
abstract = "We have determined high resolution crystal structures of the ykkC guanidine III riboswitch from Thermobifida fusca. The riboswitch forms a classic H-type pseudoknot, in which a connecting strand locates in the major groove of one duplex to form a triple helix. This is continuous with a central core of conserved nucleotides forming a left handed helical ramp of internucleotide interactions that generates the guanidinium cation binding site. The ligand is hydrogen bonded to O6 and N7 of two guanine nucleobases, and to the 2'OH of a cytidine, the nucleobase of which stacks with the guanidinium in a π-cation interaction. The binding pocket has a side opening through which a small side chain can pass, and we have determined structures with bound methylguanidine, aminoguanidine, ethylguanidine and agmatine. Comparison of this structure with those of the guanidine I and II riboswitches reveals common aspects and contrasts.",
keywords = "Gene regulation, RNA structure, X-ray crystallography, riboregulation",
author = "Lin Huang and Jia Wang and Wilson, {Timothy J.} and Lilley, {David M. J.}",
note = "We thank Saira Ashraf for RNA synthesis and acknowledge financial support from Cancer Research UK (program grant A18604). We thank Diamond for synchrotron time and the Wellcome Trust for the in-house diffractometer.",
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journal = "Cell Chemical Biology",
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The structure of the Guanidine-III Riboswitch. / Huang, Lin; Wang, Jia; Wilson, Timothy J.; Lilley, David M. J. (Lead / Corresponding author).

In: Cell Chemical Biology, Vol. 24, No. 11, 16.11.2017, p. 1407-1415.e2.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The structure of the Guanidine-III Riboswitch

AU - Huang, Lin

AU - Wang, Jia

AU - Wilson, Timothy J.

AU - Lilley, David M. J.

N1 - We thank Saira Ashraf for RNA synthesis and acknowledge financial support from Cancer Research UK (program grant A18604). We thank Diamond for synchrotron time and the Wellcome Trust for the in-house diffractometer.

PY - 2017/11/16

Y1 - 2017/11/16

N2 - We have determined high resolution crystal structures of the ykkC guanidine III riboswitch from Thermobifida fusca. The riboswitch forms a classic H-type pseudoknot, in which a connecting strand locates in the major groove of one duplex to form a triple helix. This is continuous with a central core of conserved nucleotides forming a left handed helical ramp of internucleotide interactions that generates the guanidinium cation binding site. The ligand is hydrogen bonded to O6 and N7 of two guanine nucleobases, and to the 2'OH of a cytidine, the nucleobase of which stacks with the guanidinium in a π-cation interaction. The binding pocket has a side opening through which a small side chain can pass, and we have determined structures with bound methylguanidine, aminoguanidine, ethylguanidine and agmatine. Comparison of this structure with those of the guanidine I and II riboswitches reveals common aspects and contrasts.

AB - We have determined high resolution crystal structures of the ykkC guanidine III riboswitch from Thermobifida fusca. The riboswitch forms a classic H-type pseudoknot, in which a connecting strand locates in the major groove of one duplex to form a triple helix. This is continuous with a central core of conserved nucleotides forming a left handed helical ramp of internucleotide interactions that generates the guanidinium cation binding site. The ligand is hydrogen bonded to O6 and N7 of two guanine nucleobases, and to the 2'OH of a cytidine, the nucleobase of which stacks with the guanidinium in a π-cation interaction. The binding pocket has a side opening through which a small side chain can pass, and we have determined structures with bound methylguanidine, aminoguanidine, ethylguanidine and agmatine. Comparison of this structure with those of the guanidine I and II riboswitches reveals common aspects and contrasts.

KW - Gene regulation

KW - RNA structure

KW - X-ray crystallography

KW - riboregulation

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