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Nat Chem Biol. 2014 Sep;10(9):780-6. doi: 10.1038/nchembio.1606. Epub 2014 Aug 3.

c-di-AMP binds the ydaO riboswitch in two pseudo-symmetry-related pockets.

Author information

1
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

Abstract

The ydaO riboswitch, involved in sporulation, osmotic stress responses and cell wall metabolism, targets the second messenger cyclic-di-AMP with subnanomolar affinity. We have solved the structure of c-di-AMP bound to the Thermoanaerobacter tengcongensis ydaO riboswitch, thereby identifying a five-helical scaffold containing a zippered-up bubble, a pseudoknot and long-range tertiary base pairs. Highlights include the identification of two c-di-AMP binding pockets on the same face of the riboswitch, related by pseudo-two-fold symmetry, with potential for cross-talk between sites mediated by adjacently positioned base-stacking alignments connecting pockets. The adenine rings of bound c-di-AMP molecules are wedged between bases and stabilized by stacking, base-sugar and sugar-sugar intermolecular hydrogen bonding interactions. The structural studies are complemented by isothermal titration calorimetry-based binding studies of mutants mediating key tertiary intermolecular contacts. The T. tengcongensis ydaO riboswitch, like its Bacillus subtilis counterpart, most likely functions through a transcription termination mechanism, with the c-di-AMP bound state representing an 'off' switch.

PMID:
25086509
PMCID:
PMC4217635
DOI:
10.1038/nchembio.1606
[Indexed for MEDLINE]
Free PMC Article

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