5KH8

Solution structures of the apo state fluoride riboswitch

Summary for 5KH8

• Entry DOI: 10.2210/pdb5kh8/pdb
• NMR Information: BMRB: 30108
• Descriptor: riboswitch (47-MER) (1 entity in total)
• Functional Keywords: apo state, pseudoknot, riboswitch aptamer, transcriptional regulation, rna
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 15053.96

Authors

Zhang, Q.,Zhao, B. (deposition date: 2016-06-14, release date: 2017-07-19, Last modification date: 2024-05-15)

Primary citation

Zhao, B.,Guffy, S.L.,Williams, B.,Zhang, Q.
An excited state underlies gene regulation of a transcriptional riboswitch.
Nat. Chem. Biol., 13:968-974, 2017

PubMed Abstract: Riboswitches control gene expression through ligand-dependent structural rearrangements of the sensing aptamer domain. However, we found that the Bacillus cereus fluoride riboswitch aptamer adopts identical tertiary structures in solution with and without ligand. Using chemical-exchange saturation transfer (CEST) NMR spectroscopy, we revealed that the structured ligand-free aptamer transiently accesses a low-populated (∼1%) and short-lived (∼3 ms) excited conformational state that unravels a conserved 'linchpin' base pair to signal transcription termination. Upon fluoride binding, this highly localized, fleeting process is allosterically suppressed, which activates transcription. We demonstrated that this mechanism confers effective fluoride-dependent gene activation over a wide range of transcription rates, which is essential for robust toxicity responses across diverse cellular conditions. These results unveil a novel switching mechanism that employs ligand-dependent suppression of an aptamer excited state to coordinate regulatory conformational transitions rather than adopting distinct aptamer ground-state tertiary architectures, exemplifying a new mode of ligand-dependent RNA regulation.

PubMed: 28719589
DOI: 10.1038/nchembio.2427

Experimental method

SOLUTION NMR