NF-κB p52:RelB heterodimer recognizes two classes of κB sites with two distinct modes

The X-ray structure of the nuclear factor-kappa B (NF-kappa B) p52:RelB:kappa B DNA complex reveals a new recognition feature not previously seen in other NF-kappa B:kappa B DNA complexes. Arg 125 of RelB is in contact with an additional DNA base pair. Surprisingly, the p52: RelB R125A mutant heterodimer shows defects both in DNA binding and in transcriptional activity only to a subclass of kappa B sites. We found that the Arg 125-sensitive kappa B sites contain more contiguous and centrally located A:T base pairs than do the insensitive sites. A protein-induced kink observed in this complex, which used an AT-rich kappa B site, might allow the DNA contact by Arg 125; such a kink might not be possible in complexes with non-AT-rich kappa B sites. Furthermore, we show that the p52: RelB heterodimer binds to a broader spectrum of kappa B sites when compared with the p50:RelA heterodimer. We suggest that the p52: RelB heterodimer is more adaptable to complement sequence and structural variations in kappa B sites when compared with other NF-kappa B dimers.