The crystal structure of the I kappa B alpha/NF-kappa B complex reveals mechanisms of NF-kappa B inactivation

I kappa B alpha regulates the transcription factor NF-kappa B through the f ormation of stable I kappa B alpha/NF-kappa B complexes. Prior to induction , I kappa B alpha retains NF-kappa B in the cytoplasm until the NF-kappa B activation signal is received. After activation, NF-kappa B is removed from gene promoters through association with nuclear I kappa B alpha, restoring the preinduction state. The 2.3 Angstrom crystal structure of I kappa B al pha in complex with the NF-kappa B p50/p65 heterodimer reveals mechanisms o f these inhibitory activities. The presence of I kappa B alpha allows large en bloc movement of the NF-kappa B p65 subunit amino-terminal domain. This conformational change induces allosteric inhibition of NF-kappa B DNA bind ing. Amino acid residues immediately preceding the nuclear localization sig nals of both NF-kappa B p50 and p65 subunits are tethered to the I kappa B alpha aminoterminal ankyrin repeats, impeding NF-kappa B from nuclear impor t machinery recognition.