NEMO binding domain of IKK-2 encompasses amino acids 735-745.
NF-kappaB activation is mediated by the IKK signalsome. Though this signalsome is comprised of IKK-1, IKK-2, and NEMO/IKKgamma, it is the interaction between IKK-2 and NEMO that is critical to formation of a functional signalsome. More specifically, previous reports have indicated that this interaction involves the C-terminal LDWSWL residues of IKK-2 (called the Nemo Binding Domain (NBD)) and the N-terminus of NEMO. In an effort to characterize the IKK-2:NEMO interaction, we have investigated several NBD-containing peptides for their ability to bind NEMO and inhibit the critical IKK-2:NEMO interaction. The six residue NBD peptide, LDWSWL, showed modest binding to NEMO and little inhibition of the IKK-2:NEMO interaction, whereas peptides containing the NBD plus additional flanking amino acids (NBD-containing peptides) more effectively bound NEMO and inhibited the interaction. These longer NBD-containing peptides may be required to give the NBD an appropriate conformation for recognition by NEMO and/or to provide for additional interactions with NEMO.
Strnad
Joann
J
Drug Discovery Research, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA. joann.strnad@bms.com
McDonnell
Patricia A
PA
Riexinger
Douglas J
DJ
Mapelli
Claudio
C
Cheng
Lihong
L
Gray
Hilary
H
Ryseck
Rolf P
RP
Burke
James R
JR
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051550:I-kappa B Kinase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D016328:NF-kappa B / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D018411:Spodoptera
D000596:Amino Acids; C491731:IKBKG protein, human; D016328:NF-kappa B; D010446:Peptide Fragments; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase