Structural Studies of the Purine and SAM Binding Riboswitches

Abstract

Riboswitches are recently discovered genetic regulatory elements found in the 5′-untranslated regions of bacterial mRNAs thatact through their ability to specifically bind small-molecule metabolites. Binding of the ligand to the aptamer domain of theriboswitch is communicated to a second domain, the expression platform, which directs transcription or translation of themRNA. To understand this process on a molecular level, structures of three of these riboswitches bound to their cognate ligandshave been solved by X-ray crystallography: the purine, thiamine pyrophosphate (TPP), and S-adenosylmethionine (SAM-I)binding aptamer domains. These studies have uncovered three common themes between the otherwise different molecules. First,the natural RNA aptamers recognize directly or indirectly almost every feature of their ligand to achieve extraordinary specificity.Second, all of these RNAs use a complex tertiary architecture to establish the binding pocket. Finally, in each case, ligandbinding serves to stabilize a helix that communicates the binding event to the expression platform. Here, we discuss theseproperties of riboswitches in the context of the purine and SAM-I riboswitches.