STRUCTURE OF THE HUMAN NF-KAPPA-B P52 HOMODIMER-DNA COMPLEX AT 2.1 ANGSTROM RESOLUTION

The crystal structure of human NF-kappa B p52 in its specific complex with the natural kappa B DNA binding site MHC H-2 has been solved at 2 .1 Angstrom resolution, Whereas the overall structure resembles that o f the NF-kappa B p50-DNA complex, pronounced differences are observed within the 'insert region'. This sequence segment differs in length be tween different Rel proteins. Compared with NF-kappa B p50, the compac t alpha-helical insert region element is rotated away from the core of the N-terminal domain, opening up a mainly polar cleft, The insert re gion presents potential interaction surfaces to other proteins, The hi gh resolution of the structure reveals many water molecules which medi ate interactions in the protein-DNA interface, Additional complexity i n Rel protein-DNA interaction comes from an extended interfacial water cavity that connects residues at the edge of the dimer interface to t he central DNA bases, The observed water network might account for dif ferences in binding specificity between NF-kappa B p52 and NF-kappa B p50 homodimers.