Allosteric mechanism of the V. vulnificus adenine riboswitch resolved by four-dimensional chemical mapping.

摘要: The structural interconversions that mediate the gene regulatory functions of RNA molecules may be different from classic models allostery, but relevant correlations have remained elusive in even intensively studied systems. Here, we present a four-dimensional expansion chemical mapping called lock-mutate-map-rescue (LM2R), which integrates multiple layers mutation with nucleotide-resolution mapping. This technique resolves core mechanism adenine-responsive V. vulnificus add riboswitch, paradigmatic system for both Monod-Wyman-Changeux (MWC) conformational selection and non-MWC alternatives been proposed. To discriminate amongst these models, locked each functionally important helix through designed mutations assessed formation or depletion other helices via compensatory rescue evaluated by These LM2R measurements give strong support to pre-existing predicted MWC disfavor alternative suggest additional heterogeneities general across ligand-free riboswitches.