Recognition of the bacterial second messenger cyclic diguanylate by its cognate riboswitch

Nat Struct Mol Biol. 2009 Dec;16(12):1212-7. doi: 10.1038/nsmb.1701. Epub 2009 Nov 8.

Abstract

The cyclic diguanylate (bis-(3'-5')-cyclic dimeric guanosine monophosphate, c-di-GMP) riboswitch is the first known example of a gene-regulatory RNA that binds a second messenger. c-di-GMP is widely used by bacteria to regulate processes ranging from biofilm formation to the expression of virulence genes. The cocrystal structure of the c-di-GMP responsive GEMM riboswitch upstream of the tfoX gene of Vibrio cholerae reveals the second messenger binding the RNA at a three-helix junction. The two-fold symmetric second messenger is recognized asymmetrically by the monomeric riboswitch using canonical and noncanonical base-pairing as well as intercalation. These interactions explain how the RNA discriminates against cyclic diadenylate (c-di-AMP), a putative bacterial second messenger. Small-angle X-ray scattering and biochemical analyses indicate that the RNA undergoes compaction and large-scale structural rearrangement in response to ligand binding, consistent with organization of the core three-helix junction of the riboswitch concomitant with binding of c-di-GMP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pairing
  • Crystallography, X-Ray
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / chemistry
  • Cyclic GMP / metabolism
  • Gene Expression Regulation, Bacterial*
  • Intercalating Agents
  • Models, Molecular
  • Nucleic Acid Conformation
  • RNA, Bacterial / chemistry*
  • RNA, Bacterial / metabolism*
  • Scattering, Small Angle
  • Second Messenger Systems / physiology*
  • Vibrio cholerae / physiology*

Substances

  • Intercalating Agents
  • RNA, Bacterial
  • bis(3',5')-cyclic diguanylic acid
  • Cyclic GMP