Intermolecular disulfide bond formation in the NEMO dimer requires Cys54 and Cys347.
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Herscovitch M, Comb W, Ennis T, Coleman K, Yong S, Armstead B, Kalaitzidis D, Chandani S, Gilmore TD
Intermolecular disulfide bond formation in the NEMO dimer requires Cys54 and Cys347.
Biochem Biophys Res Commun. 2008 Feb 29;367(1):103-8. doi: 10.1016/j.bbrc.2007.12.123. Epub 2007 Dec 28.
- PubMed ID
- 18164680 [ View in PubMed]
- Abstract
NEMO is an essential regulatory component of the IkappaB kinase (IKK) complex, which controls activation of the NF-kappaB signaling pathway. Herein, we show that NEMO exists as a disulfide-bonded dimer when isolated from several cell types and analyzed by SDS-polyacrylamide gel electrophoresis under non-reducing conditions. Treatment of cells with hydrogen peroxide (H(2)O(2)) induces further formation of NEMO dimers. Disulfide bond-mediated formation of NEMO dimers requires Cys54 and Cys347. The ability of these residues to form disulfide bonds is consistent with their location in a NEMO dimer structure that we generated by molecular modeling. We also show that pretreatment with H(2)O(2) decreases TNFalpha-induced IKK activity in NEMO-reconstituted cells, and that TNFalpha has a diminished ability to activate NF-kappaB DNA binding in cells reconstituted with NEMO mutant C54/347A. This study implicates NEMO as a target of redox regulation and presents the first structural model for the NEMO protein.