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Cooperative ligand binding in RNA: An illustrated guide to the glycine riboswitch

Posted on:2012-09-03Degree:Ph.DType:Dissertation
University:Yale UniversityCandidate:Butler, Ethan BenjaminFull Text:PDF
GTID:1454390011458045Subject:Biology
Abstract/Summary:
Genetic regulation allows cells to specialize and respond to changes in the environment. RNA is a necessary intermediate in the process of gene expression, and as such is a common site of regulation. Riboswitches are regulatory elements found in messenger RNAs that recognize small molecules to regulate the expression of the downstream sequences. They do this by folding into intricate three-dimensional structures that are capable of directly binding their target ligand with great specificity and affinity. The glycine riboswitch recognizes the amino acid glycine and controls genes related to glycine cleavage and carbon metabolism, as well as glycine transport. This riboswitch is unique in its use of tandem aptamer domains to recognize two ligand molecules in a cooperative fashion. Presented here is the first structure of a tandem aptamer glycine riboswitch (3.6A resolution). This structure reveals the fold necessary to recognize an extraordinarily small ligand specifically and the network of interactions that occurs between aptamers. In other cooperative systems, tertiary interactions play a key role in generating cooperativity. This network is no different, suggesting that the aptamers use these contacts between aptamers to communicate the ligand status of their binding pocket and bind cooperatively.
Keywords/Search Tags:Ligand, Glycine, Cooperative, Binding, Riboswitch
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