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

ABSTRACT

The X-ray structure of the nuclear factor-kappaB (NF-kappaB) p52RelBkappaB DNA complex reveals a new recognition feature not previously seen in other NF-kappaBkappaB DNA complexes. Arg 125 of RelB is in contact with an additional DNA base pair. Surprisingly, the p52RelB R125A mutant heterodimer shows defects both in DNA binding and in transcriptional activity only to a subclass of kappaB sites. We found that the Arg 125-sensitive kappaB sites contain more contiguous and centrally located AT base pairs than do the insensitive sites. A protein-induced kink observed in this complex, which used an AT-rich kappaB site, might allow the DNA contact by Arg 125; such a kink might not be possible in complexes with non-AT-rich kappaB sites. Furthermore, we show that the p52RelB heterodimer binds to a broader spectrum of kappaB sites when compared with the p50RelA heterodimer. We suggest that the p52RelB heterodimer is more adaptable to complement sequence and structural variations in kappaB sites when compared with other NF-kappaB dimers.