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Publication Abstract from PubMed

Cyclic dinucleotides are second messengers that target the adaptor STING and stimulate the innate immune response in mammals. Besides protein receptors, there are bacterial riboswitches that selectively recognize cyclic dinucleotides. We recently discovered a natural riboswitch that targets 3',3'-cGAMP, which is distinguished from the endogenous mammalian signal 2',3'-cGAMP by its backbone connectivity. Here, we report on structures of the aptamer domain of the 3',3'-cGAMP riboswitch from Geobacter in the 3',3'-cGAMP and c-di-GMP bound states. The riboswitch adopts a tuning fork-like architecture with a junctional ligand-binding pocket and different orientations of the arms are correlated with the identity of the bound cyclic dinucleotide. Subsequent biochemical experiments revealed that specificity of ligand recognition can be affected by point mutations outside of the binding pocket, which has implications for both the assignment and reengineering of riboswitches in this structural class.

Structural Basis for Molecular Discrimination by a 3',3'-cGAMP Sensing Riboswitch.,Ren A, Wang XC, Kellenberger CA, Rajashankar KR, Jones RA, Hammond MC, Patel DJ Cell Rep. 2015 Apr 7;11(1):1-12. doi: 10.1016/j.celrep.2015.03.004. Epub 2015 Mar, 26. PMID:25818298^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.