Structural Basis for Molecular Discrimination by a 3′,3′-cGAMP Sensing Riboswitch

• DOI: 10.1016/j.celrep.2015.03.004
• Publication Date: 2015-04-07T16:00:40Z
• Authors: Aiming Ren; Xin C. Wang; Colleen A. Kellen...; Kanagalaghatta R....; Roger A. Jones; Ming C. Hammond; Dinshaw J. Patel
• Keywords: Riboswitch; Aptamer; Second messenger system

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