Structure of an IκBα/NF-κB complex

The inhibitory protein, I kappa B alpha, sequesters the transcription factor, NF-kappa B, as an inactive complex in the cytoplasm. The structure of the I kappa B alpha ankyrin repeat domain, bound to a partially truncated NF-kappa B heterodimer (p50/p65), has been determined by X-ray crystallography at 2.7 Angstrom resolution. It shows a stack of six I kappa B alpha ankyrin repeats facing the C-terminal domains of the NF-kappa B Rel homology regions. Contacts occur in discontinuous patches, suggesting a combinatorial quality for ankyrin repeat specificity. The first two repeats cover an alpha helically ordered segment containing the p65 nuclear localization signal. The position of the sixth ankyrin repeat shows that full-length I kappa B alpha Will occlude the NF-kappa B DNA-binding cleft. The orientation of I kappa B alpha in the complex places its N- and C-terminal regions in appropriate locations for their known regulatory functions.