Structural and Functional Properties of Riboswitches

Riboswitches control gene expression by binding to small moleculemetabolites. In our lab, we use biochemical and crystallographic techniques to elucidate the structural and functional properties ofriboswitches. One of the riboswitches we are working on is the tandem glycine riboswitch. It is unique in that the two glycine aptamers bindglycines cooperatively and control downstream gene expression in a more digital manner. The exact structural mechanism for this glycinebinding cooperativity is not well understood. We hypothesize that the cooperativity is caused by the formation of Aptamer Disruptor in theabsence of glycine. RNA biochemistry techniques are used to test this model.

To understand exactly how the Aptamer Disruptor contributes to theglycine binding cooperativity and to elucidate the detailed glycine binding network, we set out to crystallize the glycine riboswitchusing a Chaperone-assisted RNA Crystallography approach [Ye et al PNAS 105, 82-7 (2008)]. We have obtained Fabs binding to the glycineriboswitches via phage display. Characterization of the affinities and specificities of these Fabs with glycine riboswitches are underinvestigation.

Future projects include structure based design to obtain novel antibiotic drugs targeting riboswitches and development of RNA antibody technologies for research and clinic applications.