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NEMO specifically recognizes K63‐linked poly‐ubiquitin chains through a new bipartite ubiquitin‐binding domain
Author(s) -
Laplantine E,
Fontan E,
Chiaravalli J,
Lopez T,
Lakisic G,
Véron M,
Agou F,
Israël Alain
Publication year - 2009
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2009.241
Subject(s) - ubiquitin , biology , ubiquitin ligase , ubiquitin protein ligases , ubiquitins , microbiology and biotechnology , plasma protein binding , deubiquitinating enzyme , domain (mathematical analysis) , dna binding protein , ubiquitin conjugating enzyme , bipartite graph , biochemistry , genetics , transcription factor , gene , mathematical analysis , graph , mathematics , discrete mathematics
An important property of NEMO, the core element of the IKK complex involved in NF‐κB activation, resides in its ability to specifically recognize poly‐ubiquitin chains. A small domain called NOA/UBAN has been suggested to be responsible for this property. We recently demonstrated that the C‐terminal Zinc Finger (ZF) of NEMO is also able to bind ubiquitin. We show here by ZF swapping and mutagenesis that this represents its only function. While neither NOA nor ZF shows any preference for K63‐linked chains, we demonstrate that together they form a bipartite high‐affinity K63‐specific ubiquitin‐binding domain. A similar domain can be found in two other proteins, Optineurin and ABIN2, and can be freely exchanged with that of NEMO without interfering with its activity. This suggests that the main function of the C‐terminal half of NEMO is to specifically bind K63‐linked poly‐ubiquitin chains. We also demonstrate that the recently described binding of NEMO to linear poly‐ubiquitin chains is dependent on the NOA alone and does not require the presence of the ZF.