Recognition of Nucleic Acids by Transcription Factor NF-κB

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NF-κB is a ubiquitous transcription factor that controls the expression of genes involved in development, inflammation, and cell survival. Since the first X-ray crystal structures revealed the DNA-binding portions of NF-κB in complex with target DNA, it has been appreciated that NF-κB exhibits a unique and complicated mechanism for DNA recognition and binding. NF-κB possesses the ability to bind to specific DNA sequences with high affinity. It accomplishes this through the action of conserved structured loops that strategically place specific DNA base-contacting amino acid side chains into register with double-stranded DNA. The bi-domain structure of the individual NF-κB subunit DNA-binding scaffolds permits degeneracy within the consensus target DNA sequence. Alternative conformations of NF-κB upon these degenerate DNA sequences directly affect target gene expression levels. The combination of ordered nucleotide base-contacting loops within a flexible domain architecture has been exploited by small folded RNA molecules that have been developed to specifically bind and inhibit NF-κB subunits.