Structural Basis for Recognition of Diubiquitins by NEMO

Journal Article · Fri Mar 27 04:00:00 EDT 2009 · Mol. Cell

DOI:https://doi.org/10.1016/j.molcel.2009.01.012· OSTI ID:1005532

Lo, Y C; Lin, S C; Rospigliosi, C C; Conze, D B; Wu, C J; Ashwell, J D; Eliezer, D; Wu, H

NEMO is the regulatory subunit of the I{kappa}B kinase (IKK) in NF-{kappa}B activation, and its CC2-LZ region interacts with Lys63 (K63)-linked polyubiquitin to recruit IKK to receptor signaling complexes. In vitro, CC2-LZ also interacts with tandem diubiquitin. Here we report the crystal structure of CC2-LZ with two dimeric coiled coils representing CC2 and LZ, respectively. Surprisingly, mutagenesis and nuclear magnetic resonance experiments reveal that the binding sites for diubiquitins at LZ are composites of both chains and that each ubiquitin in diubiquitins interacts with symmetrical NEMO asymmetrically. For tandem diubiquitin, the first ubiquitin uses the conserved hydrophobic patch and the C-terminal tail, while the second ubiquitin uses an adjacent surface patch. For K63-linked diubiquitin, the proximal ubiquitin uses its conserved hydrophobic patch, while the distal ubiquitin mostly employs the C-terminal arm including the K63 linkage residue. These studies uncover the energetics and geometry for mutual recognition of NEMO and diubiquitins.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: USDOE
• OSTI ID: 1005532
• Journal Information: Mol. Cell, Journal Name: Mol. Cell Journal Issue: (5) ; 03, 2009 Vol. 33; ISSN 1097-2765
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
CHAINS
CRYSTAL STRUCTURE
GEOMETRY
IN VITRO
MUTAGENESIS
NUCLEAR MAGNETIC RESONANCE
PHOSPHOTRANSFERASES