Structural Basis for Recognition of Diubiquitins by NEMO

Yu Chih Lo, Su Chang Lin, Carla C. Rospigliosi, Dietrich B. Conze, Chuan Jin Wu, Jonathan D. Ashwell, David Eliezer, Hao Wu

研究成果: Article同行評審

200 引文 斯高帕斯(Scopus)


NEMO is the regulatory subunit of the IκB kinase (IKK) in NF-κB 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.

頁(從 - 到)602-615
期刊Molecular Cell
出版狀態Published - 2009 3月 13

All Science Journal Classification (ASJC) codes

  • 分子生物學
  • 細胞生物學


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