STRUCTURE |
Binding of an RNA aptamer makes a protein spread its wings
A new crystal structure of an RNA aptamer (protein-binding oligonucleotide) with the transcription factor NF-B marks the first time that both RNA- and DNA-bound structures of the same transcription factor have been known. The structure--determined and analyzed by L. James Maher III of the Mayo Foundation, in Rochester, Minn.; Gourisankar Ghosh of the University of California, San Diego; and coworkers--could aid in the design of aptamers for gene regulation [Proc. Natl. Acad. Sci. USA, 100, 9268 (2003)]. The study shows that one RNA aptamer (space-filling structure in figure) binds to each subunit of homodimeric NF-B (ribbon structure). The dimer makes a major conformational change to an unprecedented wingspread butterfly-like structure in response to aptamer binding. And the RNAs bind to the same amino acids normally in contact with genomic DNA when NF-B acts as a transcription factor. Small molecules that stabilize this altered protein conformation might provide a novel approach to inhibition of NF-B, a key regulator of inflammation in the body.
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