Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 16, Issue 12, Pages 1212-1217Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.1701
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Funding
- US Department of Energy
- Basic Energy Sciences
- Office of Science [W-31-109-ENG-38]
- US National Institutes of Health [RR-08630]
- Howard Hughes Medical Institute (HHMI)
- W.M. Keck Foundation
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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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