Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 385, Issue 3, Pages 938-948Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2008.10.074
Keywords
RNA-ligand interaction; riboswitch; X-ray crystallography; isothermal titration calorimetry; noncoding RNA
Categories
Funding
- National Institutes of Health [GM 073850]
- National Institutes of Health Predoctoral Training [T32 GM-065103]
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Riboswitches are noncoding RNA elements that are commonly found in the 5'-untranslated region of bacterial mRNA. Binding of a small-molecule metabolite to the riboswitch aptamer domain guides the folding of the downstream sequence into one of two mutually exclusive secondary structures that directs gene expression. The purine riboswitch family, which regulates aspects of purine biosynthesis and transport, contains three distinct classes that specifically recognize guanine/hypoxanthine, adenine, or 2'-deoxyguanosine (dG). Structural analysis of the guanine and adenine classes revealed a binding pocket that almost completely buries the nucleobase within the core of the folded RNA. Thus, it is somewhat surprising that this family of RNA elements also recognizes dG. We have used a combination of structural and biochemical techniques to understand how the guanine riboswitch could be converted into a dG binder and the structural basis for dG recognition. These studies reveal that a limited number of sequence changes to a guanine-sensing RNA are required to cause a specificity switch from guanine to 2'-deoxyguanosine, and to impart an altered structure for accommodating the additional deoxyribose sugar moiety. (C) 2008 Elsevier Ltd. All rights reserved.
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