Recognition of the bacterial second messenger cyclic diguanylate by its cognate riboswitch.
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.
Kulshina
Nadia
N
Molecular and Cellular Biology Program, University of Washington, Seattle, Washington, USA.
Baird
Nathan J
NJ
Ferré-D'Amaré
Adrian R
AR
D020029:Base Pairing; D018360:Crystallography, X-Ray; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D007364:Intercalating Agents; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D012329:RNA, Bacterial / Q000737:chemistry* / Q000378:metabolism*; D053838:Scattering, Small Angle; D015290:Second Messenger Systems / Q000502:physiology*; D014734:Vibrio cholerae / Q000502:physiology*
D007364:Intercalating Agents; D012329:RNA, Bacterial; C062025:bis(3',5')-cyclic diguanylic acid; D006152:Cyclic GMP