2ZVO

NEMO CoZi domain in complex with diubiquitin in C2 space group

Summary for 2ZVO

• Entry DOI: 10.2210/pdb2zvo/pdb
• Related: 2ZVN 3F89
• Descriptor: UBC protein, NF-kappa-B essential modulator (3 entities in total)
• Functional Keywords: nf-kb signaling, ubiquitin binding, coiled coil, cytoplasm, metal-binding, nucleus, phosphoprotein, transcription, transcription regulation, ubl conjugation, zinc, zinc-finger, transcription-signaling protein complex, transcription/signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm : O88522
• Total number of polymer chains: 4
• Total formula weight: 55911.87

Authors

Rahighi, S.,Ikeda, F.,Kawasaki, M.,Akutsu, M.,Suzuki, N.,Kato, R.,Kensche, T.,Uejima, T.,Bloor, S.,Komander, D.,Randow, F.,Wakatsuki, S.,Dikic, I. (deposition date: 2008-11-12, release date: 2009-03-24, Last modification date: 2024-05-29)

Primary citation

Rahighi, S.,Ikeda, F.,Kawasaki, M.,Akutsu, M.,Suzuki, N.,Kato, R.,Kensche, T.,Uejima, T.,Bloor, S.,Komander, D.,Randow, F.,Wakatsuki, S.,Dikic, I.
Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation
Cell(Cambridge,Mass.), 136:1098-1109, 2009

PubMed Abstract: Activation of nuclear factor-kappaB (NF-kappaB), a key mediator of inducible transcription in immunity, requires binding of NF-kappaB essential modulator (NEMO) to ubiquitinated substrates. Here, we report that the UBAN (ubiquitin binding in ABIN and NEMO) motif of NEMO selectively binds linear (head-to-tail) ubiquitin chains. Crystal structures of the UBAN motif revealed a parallel coiled-coil dimer that formed a heterotetrameric complex with two linear diubiquitin molecules. The UBAN dimer contacted all four ubiquitin moieties, and the integrity of each binding site was required for efficient NF-kappaB activation. Binding occurred via a surface on the proximal ubiquitin moiety and the canonical Ile44 surface on the distal one, thereby providing specificity for linear chain recognition. Residues of NEMO involved in binding linear ubiquitin chains are required for NF-kappaB activation by TNF-alpha and other agonists, providing an explanation for the detrimental effect of NEMO mutations in patients suffering from X-linked ectodermal dysplasia and immunodeficiency.

PubMed: 19303852
DOI: 10.1016/j.cell.2009.03.007

Experimental method

X-RAY DIFFRACTION (2.9 Å)