3FX0

Crystal structure of Human NEMO CC2_LZ domain

3FX0 の概要

• エントリーDOI: 10.2210/pdb3fx0/pdb
• 分子名称: NF-kappa-B essential modulator (1 entity in total)
• 機能のキーワード: 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
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : Q9Y6K9
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22149.24

構造登録者

Lo, Y.C.,Lin, S.C.,Wu, H. (登録日: 2009-01-19, 公開日: 2009-04-07, 最終更新日: 2024-02-21)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3.2 Å)