Structural basis for functional versatility in riboswitches.

9780438194540

Ann Arbor : ProQuest Dissertations & Theses, 2018

1 online resource (167 p.)

Access is available to the Yale community.

Since the discovery of tRNA in 1957, it has been demonstrated in the literature that RNA performs catalysis, uses cofactors, binds ligands with high affinity and stringency, and can readily evolve new functions under selective pressure. The versatility of RNA is exemplified by a class of riboswitches known as the ykkC RNA motif, which is a single RNA scaffold that has evolved to bind multiple, dissimilar ligands. In my dissertation, I present the structural basis of how this class of RNAs recognizes guanidine, phosphoribosyl pyrophosphate (PRPP), or guanosine tetra- and pentaphosphate ((p)ppGpp) with high affinity and specificity through changes in only a few critical residues in the ligand binding pocket. The RNA uses a combination of altering the precise location of the binding pocket and also manipulating a long-range base pair located in an S-turn motif to change base pairing in the binding pocket, all while maintaining a similar overall structure. I also present the structure of a second class of guanidine riboswitch known as the mini-ykkC RNA, which has a dramatically different tertiary structure from the guanidine-I riboswitch. This RNA utilizes the same types of interactions at the level of the binding pocket to recognize the guanidinium cation, but the overall structure is dramatically different. Finally, I present data suggesting that the specificity of the ZMP/ZTP riboswitch for Z nucleotides over adenosine nucleotides is partially accomplished through the use of the binding pocket magnesium ion. Together, these data showcase the versatility of RNA.

Books / Online / Dissertations & Theses

English

January 09, 2019

Thesis (Ph.D.)--Yale University, 2018.

Yale University.