A non-canonical UBA-UBL interaction forms the linear-ubiquitin-chain assembly complex

EMBO Rep. 2012 May 1;13(5):462-8. doi: 10.1038/embor.2012.24.


HOIL-1L and its binding partner HOIP are essential components of the E3-ligase complex that generates linear ubiquitin (Ub) chains, which are critical regulators of NF-κB activation. Using crystallographic and mutational approaches, we characterize the unexpected structural basis for the specific interaction between the Ub-like domain (UBL) of HOIL-1L and the Ub-associated domain (UBA) of HOIP. Our data indicate the functional significance of this non-canonical mode of UBA-UBL interaction in E3 complex formation and subsequent NF-κB activation. This study highlights the versatility and specificity of protein-protein interactions involving Ub/UBLs and their cognate proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism
  • Cell Line
  • Circular Dichroism
  • Humans
  • Immunoprecipitation
  • Magnetic Resonance Spectroscopy
  • NF-kappa B / metabolism
  • Protein Binding
  • Protein Structure, Secondary
  • Surface Plasmon Resonance
  • Transcription Factors
  • Ubiquitin / chemistry*
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligases / chemistry*
  • Ubiquitin-Protein Ligases / metabolism*
  • Ultracentrifugation


  • Carrier Proteins
  • NF-kappa B
  • Transcription Factors
  • Ubiquitin
  • RBCK1 protein, human
  • RNF31 protein, human
  • Ubiquitin-Protein Ligases