title: Structural basis for diversity in the SAM clan of riboswitches.
abstract: In bacteria, sulfur metabolism is regulated in part by seven known families of riboswitches that bind S-adenosyl-l-methionine (SAM). Direct binding of SAM to these mRNA regulatory elements governs a downstream secondary structural switch that communicates with the transcriptional and/or translational expression machinery. The most widely distributed SAM-binding riboswitches belong to the SAM clan, comprising three families that share a common SAM-binding core but differ radically in their peripheral architecture. Although the structure of the SAM-I member of this clan has been extensively studied, how the alternative peripheral architecture of the other families supports the common SAM-binding core remains unknown. We have therefore solved the X-ray structure of a member of the SAM-I/IV family containing the alternative "PK-2" subdomain shared with the SAM-IV family. This structure reveals that this subdomain forms extensive interactions with the helix housing the SAM-binding pocket, including a highly unusual mode of helix packing in which two helices pack in a perpendicular fashion. Biochemical and genetic analysis of this RNA reveals that SAM binding induces many of these interactions, including stabilization of a pseudoknot that is part of the regulatory switch. Despite strong structural similarity between the cores of SAM-I and SAM-I/IV members, a phylogenetic analysis of sequences does not indicate that they derive from a common ancestor.
authors.affiliation: Department of Chemistry and Biochemistry and Howard Hughes Medical Institute, University of Colorado, Boulder, CO, 80309-0596.
authors.forename: Jeremiah J
authors.initials: JJ
authors.lastname: Trausch
authors.forename: Zhenjiang
authors.initials: Z
authors.lastname: Xu
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Edwards
authors.forename: Francis E
authors.initials: FE
authors.lastname: Reyes
authors.forename: Phillip E
authors.initials: PE
authors.lastname: Ross
authors.forename: Rob
authors.initials: R
authors.lastname: Knight
authors.forename: Robert T
authors.initials: RT
authors.lastname: Batey
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001419:Bacteria / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D015964:Gene Expression Regulation, Bacterial; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D020871:RNA Stability; D012329:RNA, Bacterial / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D058928:Riboswitch / Q000235:genetics*; D012436:S-Adenosylmethionine / Q000378:metabolism*
chemical_list: D052157:Aptamers, Nucleotide; D012329:RNA, Bacterial; D012333:RNA, Messenger; D058928:Riboswitch; D012436:S-Adenosylmethionine
keywords: RNA structure; X-ray crystallography; chemical probing; gene regulation; isothermal titration calorimetry
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