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Proc Natl Acad Sci U S A. 2014 May 6;111(18):6624-9. doi: 10.1073/pnas.1312918111. Epub 2014 Apr 21.

Structural basis for diversity in the SAM clan of riboswitches.

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Department of Chemistry and Biochemistry and Howard Hughes Medical Institute, University of Colorado, Boulder, CO, 80309-0596.


In bacteria, sulfur metabolism is regulated in part by seven known families of riboswitches that bind S-adenosyl-l-methionine (SAM). Direct binding of SAM to these mRNA regulatory elements governs a downstream secondary structural switch that communicates with the transcriptional and/or translational expression machinery. The most widely distributed SAM-binding riboswitches belong to the SAM clan, comprising three families that share a common SAM-binding core but differ radically in their peripheral architecture. Although the structure of the SAM-I member of this clan has been extensively studied, how the alternative peripheral architecture of the other families supports the common SAM-binding core remains unknown. We have therefore solved the X-ray structure of a member of the SAM-I/IV family containing the alternative "PK-2" subdomain shared with the SAM-IV family. This structure reveals that this subdomain forms extensive interactions with the helix housing the SAM-binding pocket, including a highly unusual mode of helix packing in which two helices pack in a perpendicular fashion. Biochemical and genetic analysis of this RNA reveals that SAM binding induces many of these interactions, including stabilization of a pseudoknot that is part of the regulatory switch. Despite strong structural similarity between the cores of SAM-I and SAM-I/IV members, a phylogenetic analysis of sequences does not indicate that they derive from a common ancestor.


RNA structure; X-ray crystallography; chemical probing; gene regulation; isothermal titration calorimetry

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