3FX0

Crystal structure of Human NEMO CC2_LZ domain

Summary for 3FX0

• Entry DOI: 10.2210/pdb3fx0/pdb
• Descriptor: NF-kappa-B essential modulator (1 entity in total)
• Functional Keywords: coiled-coil, coiled coil, cytoplasm, disease mutation, ectodermal dysplasia, host-virus interaction, metal-binding, nucleus, osteopetrosis, phosphoprotein, transcription, transcription regulation, ubl conjugation, zinc, zinc-finger, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : Q9Y6K9
• Total number of polymer chains: 2
• Total formula weight: 22149.24

Authors

Lo, Y.C.,Lin, S.C.,Wu, H. (deposition date: 2009-01-19, release date: 2009-04-07, Last modification date: 2024-02-21)

Primary citation

Lo, Y.C.,Lin, S.C.,Rospigliosi, C.C.,Conze, D.B.,Wu, C.J.,Ashwell, J.D.,Eliezer, D.,Wu, H.
Structural basis for recognition of diubiquitins by NEMO.
Mol.Cell, 33:602-615, 2009

PubMed Abstract: NEMO is the regulatory subunit of the IkappaB kinase (IKK) in NF-kappaB 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.

PubMed: 19185524
DOI: 10.1016/j.molcel.2009.01.012

Experimental method

X-RAY DIFFRACTION (3.2 Å)