The crystal structure of the NF-kappa B p65 (RelA) homodimer in complex with a
DNA target has been determined to 2.4 A resolution. The two p65 subunits are not
symmetrically disposed on the DNA target. The homodimer should optimally bind to
a pseudo-palindromic nine base pair target with each subunit recognizing a
5'GGAA-3' half site separated by a central A-T base pair. However, one of the
subunits (subunit B) encounters a half site of 5'-GAAA-3'. The single base-pair
change from G-C to A-T results in highly unfavorable interactions between this
half site and the base contacting protein residues in subunit B, which leads to
an 18 degrees rotation of the N-terminal terminal domain from its normal
conformation. Remarkably, subunit B retains all the interactions with the sugar
phosphate backbone of the DNA target. This mode of interaction allows the
NF-kappa B p65 homodimer to recognize DNA targets containing only one cognate
half site. Differences in the sequence of the other half site provide variations
in conformation and affinity of the complex.
