Chemical basis of glycine riboswitch cooperativity

Kwon, Man Jae; Strobel, Scott A.

doi:10.1261/rna.771608

Cited by 73 publications

(130 citation statements)

References 38 publications

(40 reference statements)

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“…Determining glycine riboswitch mutants with altered glycine affinity and cooperativity NAIM studies identified several asymmetric interference sites distributed between aptamers 1 and 2 of the glycine riboswitch from Vibrio cholerae (VC) (Kwon and Strobel 2008). These interference sites provided good candidates for residues potentially involved in asymmetric cooperative interactions between the two aptamers.…”

Section: Resultsmentioning

confidence: 99%

“…The asymmetric interference pattern suggested that the minor groove of P1 in aptamer 1 is a site of tertiary interaction facilitating cooperativity between the aptamers (Kwon and Strobel 2008). We therefore introduced a mutation to this region and measured the binding affinity and cooperativity using in-line probing to obtain the apparent K d and Hill coefficient (n), respectively (Table 1; Regulski and Breaker 2008).…”

Section: Resultsmentioning

confidence: 99%

“…We therefore introduced a mutation to this region and measured the binding affinity and cooperativity using in-line probing to obtain the apparent K d and Hill coefficient (n), respectively (Table 1; Regulski and Breaker 2008). NAIM experiments showed N-methyl G interference at G127, which suggested that the exocyclic amine of the nucleotide could be involved in minor groove hydrogenbonding interactions (Rife et al 1998;Kwon and Strobel 2008). When C12 was mutated to a U to produce a U d G wobble pair, the riboswitch also showed a loss in cooperativity (n = 1.1) compared with wild-type (n = 1.5) ( Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…Two additional mutations were previously reported. Mutation of G127 to A, which removes the minor groove exocyclic amine, resulted in a loss of cooperativity (n = 1.1) (Kwon and Strobel 2008). To determine that the identity of the base pair was specific to aptamer 1, a C-G to U-A mutation was introduced to the P1 stem of aptamer 2.…”

Section: Resultsmentioning

confidence: 99%

“…Nucleotide analog interference mapping (NAIM) was used to investigate the chemical basis of glycine riboswitch cooperativity. This provided the framework for making and testing riboswitch mutants with altered cooperativity (Kwon and Strobel 2008). Hydroxyl radical footprinting and small-angle X-ray scattering (SAXS) have provided information on the structural transitions that occur upon riboswitch folding and ligand binding (Lipfert et al 2007).…”

Section: Introductionmentioning

confidence: 99%

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Identification of a tertiary interaction important for cooperative ligand binding by the glycine riboswitch

Erion¹,

Strobel²

2010

RNA

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The glycine riboswitch has a tandem dual aptamer configuration, where each aptamer is a separate ligand-binding domain, but the aptamers function together to bind glycine cooperatively. We sought to understand the molecular basis of glycine riboswitch cooperativity by comparing sites of tertiary contacts in a series of cooperative and noncooperative glycine riboswitch mutants using hydroxyl radical footprinting, in-line probing, and native gel-shift studies. The results illustrate the importance of a direct or indirect interaction between the P3b hairpin of aptamer 2 and the P1 helix of aptamer 1 in cooperative glycine binding. Furthermore, our data support a model in which glycine binding is sequential; where the binding of glycine to the second aptamer allows tertiary interactions to be made that facilitate binding of a second glycine molecule to the first aptamer. These results provide insight into cooperative ligand binding in RNA macromolecules.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of a tertiary interaction important for cooperative ligand binding by the glycine riboswitch

Erion¹,

Strobel²

2010

RNA

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Inhibitors Targeting Riboswitches and Ribozymes

et al. 2013

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Evidence accumulated over the past few decades has overshadowed the central role\ud traditionally attributed to proteins in biological function and placed instead the\ud RNA at the core of all fundamental biological processes. For instance, small RNA\ud domains, such as riboswitches and ribozymes, have been shown to play important,\ud if not essential, roles in a variety of cell functions, including regulation of gene\ud expression. Currently, a large number of clinically relevant antibiotics target the\ud ribosome, in particular its functional RNA component [1–4]; this indicates that,\ud owing to its structural characteristics and complexity, the RNA is a suitable\ud and efficient target for functional inhibition by small molecules. Similar to the\ud interaction of proteins with small molecular ligands, the complex 3D structure\ud of the RNA offers binding pockets and surfaces that provide hydrogen bonding,\ud base stacking, ion pairing, and hydrophobic interactions for the specific binding\ud of diverse compounds. In light of these premises, it is tempting to venture into\ud novel paths in antibiotic research by exploiting small, functional RNA elements\ud such as riboswitches and ribozymes as alternative targets for the design of novel\ud antimicrobial compounds

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Riboswitches: Ancient and Promising Genetic Regulators

et al. 2009

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Bait and switch: Metabolite‐sensing riboswitches make use of RNA structural modulation to regulate gene expression, as illustrated in the scheme, in response to subtle changes in metabolite concentrations. This review describes the current knowledge about naturally occurring riboswitches and their growing potential as antibacterial cellular targets and as molecular biosensors.magnified imageNewly discovered metabolite‐sensing riboswitches have revealed that cellular processes extensively make use of RNA structural modulation to regulate gene expression in response to subtle changes in metabolite concentrations. Riboswitches are involved at various regulation levels of gene expression, such as transcription attenuation, translation initiation, mRNA splicing and mRNA processing. Riboswitches are found in the three kingdoms of life, and in various cases, are involved in the regulation of essential genes, which makes their regulation an essential part of cell survival. Because riboswitches operate without the assistance of accessory proteins, they are believed to be remnants of an ancient time, when gene regulation was strictly based on RNA, from which are left numerous “living molecular fossils”, as exemplified by ribozymes, and more spectacularly, by the ribosome. Due to their nature, riboswitches hold high expectations for the manipulation of gene expression and the detection of small metabolites, and also offer an unprecedented potential for the discovery of novel classes of antimicrobial agents.

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Chemical basis of glycine riboswitch cooperativity

Cited by 73 publications

References 38 publications

Identification of a tertiary interaction important for cooperative ligand binding by the glycine riboswitch

Identification of a tertiary interaction important for cooperative ligand binding by the glycine riboswitch

Inhibitors Targeting Riboswitches and Ribozymes

Riboswitches: Ancient and Promising Genetic Regulators

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