Work by Mike May, now at U. Penn., revealed the NEMO binding domain (NBD) that is required for IKK binding to NEMO. While the region of NEMO that interacts with IKK is less well defined, the region of IKK that binds to NEMO can be mapped to a short amino acid sequence (indicated by the pink highlighting at right). Mutation of key tryptophan residues within this sequence abolishes NEMO/IKK interaction and signaling to NF-kB.

 

As a result of this work it was found that recombinant NBD peptide (purple) is capable of inhibiting the interaction between IKK (blue) and NEMO (green). Furthermore, when attached to a cell-permeable motif, NBD peptide can be used to interfere with the IKK complex both in vitro and in vivo, inhibiting signaling to NF-kB.

for an extensive discussion of therapeutic approaches to target NF-kB see the references at left and chapter 10 in "Handbook of Transcription Factor NF-kappa B"