Intermolecular disulfide bond formation in the NEMO dimer requires Cys54 and Cys347

被引：63

作者：

Herscovitch, Melanie ^{[1
]}

Comb, William ^{[1
]}

Ennis, Thomas ^{[1
]}

Coleman, Kate ^{[1
]}

Yong, Sheila ^{[1
]}

Armstead, Brinda ^{[1
]}

Kalaitzidis, Demetrios ^{[1
]}

Chandani, Sushil ^{[1
]}

Gilmore, Thomas D. ^{[1
]}

机构：

[1] Boston Univ, Dept Biol, Boston, MA 02215 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 367卷 / 01期

关键词：

NEMO; disulfide bond; NF-kappa B; IKK; hydrogen peroxide; cysteine; molecular modeling;

D O I：

10.1016/j.bbrc.2007.12.123

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

NEMO is an essential regulatory component of the I kappa B kinase (IKK) complex, which controls activation of the NF-kappa B 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 (14202) 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 H2O2 decreases TNF alpha-induced IKK activity in NEMO-reconstituted cells, and that TNF alpha has a diminished ability to activate NF-kappa B 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. (C) 2007 Elsevier Inc. All rights reserved.

引用

页码：103 / 108

页数：6

共 21 条

[1] The trimerization domain of nemo is composed of the interacting C-terminal CC2 and LZ coiled-coil subdomains [J].