X-ray crystal structure of an IκBβ·NF-κB p65 homodimer complex

Abstract

We report the crystal structure of a murine IκBβ·NF-κB p65 homodimer complex. Crystallographic models were determined for two triclinic crystalline systems and refined against data at 2.5 and 2.1 Å. The overall complex structure is similar to that of the IκBα·NF-κB p50/p65 heterodimer complex. One NF-κB p65 subunit nuclear localization signal clearly contacts IκBβ, whereas a homologous segment from the second subunit of the homodimer is mostly solvent-exposed. The unique 47-amino acid insertion between ankyrin repeats three and four of IκBβ is mostly disordered in the structure. Primary sequence analysis and differences in the mode of binding at the IκBβ sixth ankyrin repeat and NF-κB p65 homodimer suggest a model for nuclear IκBβ·NF-κB·DNA ternary complex formation. These unique structural features of IκBβ may contribute to its ability to mediate persistent NF-κB activation.