The crystal structure of the IkappaBalpha/NF-kappaB complex reveals mechanisms of NF-kappaB inactivation

Cell. 1998 Dec 11;95(6):759-70. doi: 10.1016/s0092-8674(00)81699-2.


IkappaBalpha regulates the transcription factor NF-kappaB through the formation of stable IkappaBalpha/NF-kappaB complexes. Prior to induction, IkappaBalpha retains NF-kappaB in the cytoplasm until the NF-kappaB activation signal is received. After activation, NF-kappaB is removed from gene promoters through association with nuclear IkappaBalpha, restoring the preinduction state. The 2.3 A crystal structure of IkappaBalpha in complex with the NF-kappaB p50/p65 heterodimer reveals mechanisms of these inhibitory activities. The presence of IkappaBalpha allows large en bloc movement of the NF-kappaB p65 subunit amino-terminal domain. This conformational change induces allosteric inhibition of NF-kappaB DNA binding. Amino acid residues immediately preceding the nuclear localization signals of both NF-kappaB p50 and p65 subunits are tethered to the IkappaBalpha amino-terminal ankyrin repeats, impeding NF-kappaB from nuclear import machinery recognition.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Dimerization
  • I-kappa B Proteins*
  • Molecular Sequence Data
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / chemistry*
  • NF-kappa B / metabolism
  • NF-kappa B p50 Subunit
  • Nuclear Localization Signals
  • Peptides / metabolism
  • Protein Conformation
  • Transcription Factor RelA


  • DNA-Binding Proteins
  • I-kappa B Proteins
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • Nuclear Localization Signals
  • Peptides
  • Transcription Factor RelA
  • NF-KappaB Inhibitor alpha
  • DNA

Associated data

  • PDB/1IKN