Cooperative and directional folding of the preQ1 riboswitch aptamer domain.

ABSTRACT: Riboswitches are cis-acting RNA fragments that regulate gene expression by sensing cellular levels of the associated small metabolites. In bacteria, the class I preQ(1) riboswitch allows the fine-tuning of queuosine biosynthesis in response to the intracellular concentration of the queuosine anabolic intermediate preQ(1). When binding preQ(1), the aptamer domain undergoes a significant degree of secondary and tertiary structural rearrangement and folds into an H-type pseudoknot. Conformational "switching" of the riboswitch aptamer domain upon recognizing its cognate metabolite plays a key role in the regulatory mechanism of the preQ(1) riboswitch. We investigate the folding mechanism of the preQ(1) riboswitch aptamer domain using all-atom Go?-model simulations. The folding pathway of such a single domain is found to be cooperative and sequentially coordinated, as the folding proceeds in the 5' ? 3' direction. This kinetically efficient folding mechanism suggests a fast ligand-binding response in competition with RNA elongation.

SUBMITTER: Feng J 

PROVIDER: S-EPMC3109358 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature