Making the Switch

Abstract

Riboswitches are regions of untranslated messenger RNA that switch their conformations when they bind specific metabolites to regulate the expression of proteins involved in the biosynthesis of the bound metabolites. For example, in bacteria, archaea, and eukaryotes, the production of the essential cofactor thiamine pyrophosphate (TPP) is tightly regulated by TPP-binding riboswitches. Thore et al. determined the structure of the eukaryotic Arabidopsis thaliana TPP riboswitch bound to TPP at 2.9 angstrom resolution. The structure shows how the bound "off" conformation, which suppresses expression of a gene involved in TPP biosynthesis, is stabilized. TPP riboswitches are attractive targets for antimicrobial drugs, and the structure rationalizes the mechanism of resistance to the antibiotic pyrithiamine. S. Thore, M. Leibundgut, N. Ban, Structure of the eukaryotic thiamine pyrophosphate riboswitch with its regulatory ligand. Science 312, 1208-1211 (2006). [Abstract] [Full Text]