title: Idiosyncratically tuned switching behavior of riboswitch aptamer domains revealed by comparative small-angle X-ray scattering analysis.
abstract: Riboswitches are structured mRNA elements that regulate gene expression upon binding specific cellular metabolites. It is thought that the highly conserved metabolite-binding domains of riboswitches undergo conformational change upon binding their cognate ligands. To investigate the generality of such a mechanism, we employed small-angle X-ray scattering (SAXS). We probed the nature of the global metabolite-induced response of the metabolite-binding domains of four different riboswitches that bind, respectively, thiamine pyrophosphate (TPP), flavin mononucleotide (FMN), lysine, and S-adenosyl methionine (SAM). We find that each RNA is unique in its global structural response to metabolite. Whereas some RNAs exhibit distinct free and bound conformations, others are globally insensitive to the presence of metabolite. Thus, a global conformational change of the metabolite-binding domain is not a requirement for riboswitch function. It is possible that the range of behaviors observed by SAXS, rather than being a biophysical idiosyncrasy, reflects adaptation of riboswitches to the regulatory requirements of their individual genomic context.
authors.affiliation: Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Baird
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Ferré-D'Amaré
mesh_terms: D052157:Aptamers, Nucleotide; D001419:Bacteria / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005486:Flavin Mononucleotide / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D009690:Nucleic Acid Conformation; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics; D038621:Regulatory Sequences, Ribonucleic Acid; D012436:S-Adenosylmethionine / Q000378:metabolism; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
chemical_list: D052157:Aptamers, Nucleotide; D012333:RNA, Messenger; D038621:Regulatory Sequences, Ribonucleic Acid; D012436:S-Adenosylmethionine; D005486:Flavin Mononucleotide; D008274:Magnesium; D008239:Lysine