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

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

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  • 1Molecular and Cellular Biology Program, University of Washington, Seattle, Washington, USA.

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.

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  • Come together, right now. [Nat Struct Mol Biol. 2009]
PMID:
19898478
[PubMed - indexed for MEDLINE]
PMCID:
PMC2925111
Free PMC Article

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