Structure and ligand binding of the SAM-V riboswitch

Lin Huang, David M. J. Lilley (Lead / Corresponding author)

Research output: Contribution to journalArticle

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55 Downloads (Pure)

Abstract

SAM-V is one of the class of riboswitches that bind S-adenosylmethione, regulating gene expression by controlling translation. We have solved the crystal structure of the metY SAM-V riboswitch bound to its SAM ligand at 2.5 Å resolution. The RNA folds as an H-type pseudoknot, with a major-groove triple helix in which resides the SAM ligand binding site. The bound SAM adopts an elongated conformation aligned with the axis of the triple helix, and is held at either end by hydrogen bonding to the adenine and the amino acid moieties. The central sulfonium cation makes electrostatic interactions with an U:A.U base triple, so conferring specificity. We propose a model in which SAM binding leads to association of the triplex third strand that stabilizes a short helix and occludes the ribosome binding site. Thus the new structure explains both ligand specificity and the mechanism of genetic control.

Original languageEnglish
Pages (from-to)6869-6879
Number of pages11
JournalNucleic Acids Research
Volume46
Issue number13
Early online date21 Jun 2018
DOIs
Publication statusPublished - 27 Jul 2018

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Riboswitch
Ligands
Binding Sites
Adenine
Hydrogen Bonding
Static Electricity
Ribosomes
Cations
RNA
Gene Expression
Amino Acids

Cite this

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abstract = "SAM-V is one of the class of riboswitches that bind S-adenosylmethione, regulating gene expression by controlling translation. We have solved the crystal structure of the metY SAM-V riboswitch bound to its SAM ligand at 2.5 {\AA} resolution. The RNA folds as an H-type pseudoknot, with a major-groove triple helix in which resides the SAM ligand binding site. The bound SAM adopts an elongated conformation aligned with the axis of the triple helix, and is held at either end by hydrogen bonding to the adenine and the amino acid moieties. The central sulfonium cation makes electrostatic interactions with an U:A.U base triple, so conferring specificity. We propose a model in which SAM binding leads to association of the triplex third strand that stabilizes a short helix and occludes the ribosome binding site. Thus the new structure explains both ligand specificity and the mechanism of genetic control.",
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Structure and ligand binding of the SAM-V riboswitch. / Huang, Lin; Lilley, David M. J. (Lead / Corresponding author).

In: Nucleic Acids Research, Vol. 46, No. 13, 27.07.2018, p. 6869-6879.

Research output: Contribution to journalArticle

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AU - Huang, Lin

AU - Lilley, David M. J.

N1 - Cancer Research UK [A18604]. The open access publication charge for this paper has been waived by Oxford University Press–NAR Editorial Board members are entitled to one free paper per year in recognition of their work on behalf of the journal.

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