SNAP output for PDB entry 4w92 [SNAP web server]

PDB-id

4w92; SNAP-derived features in text and JSON formats; DNAproDB

Class

RNA binding protein-RNA

Method

X-ray (3.209 Å)

Summary

Crystal structure of bacillus subtilis cyclic-di-amp riboswitch ydao

Reference

Jones CP, Ferre-D'Amare AR (2014): "Crystal structure of a c-di-AMP riboswitch reveals an internally pseudo-dimeric RNA." Embo J., 33, 2692-2703. doi: 10.15252/embj.201489209.

Abstract

Cyclic diadenosine monophosphate (c-di-AMP) is a second messenger that is essential for growth and homeostasis in bacteria. A recently discovered c-di-AMP-responsive riboswitch controls the expression of genes in a variety of bacteria, including important pathogens. To elucidate the molecular basis for specific binding of c-di-AMP by a gene-regulatory mRNA domain, we have determined the co-crystal structure of this riboswitch. Unexpectedly, the structure reveals an internally pseudo-symmetric RNA in which two similar three-helix-junction elements associate head-to-tail, creating a trough that cradles two c-di-AMP molecules making quasi-equivalent contacts with the riboswitch. The riboswitch selectively binds c-di-AMP and discriminates exquisitely against other cyclic dinucleotides, such as c-di-GMP and cyclic-AMP-GMP, via interactions with both the backbone and bases of its cognate second messenger. Small-angle X-ray scattering experiments indicate that global folding of the riboswitch is induced by the two bound cyclic dinucleotides, which bridge the two symmetric three-helix domains. This structural reorganization likely couples c-di-AMP binding to gene expression.