Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne

Nat Struct Mol Biol. 2010 Aug;17(8):939-47. doi: 10.1038/nsmb.1873. Epub 2010 Jul 11.


Ubiquitin is a versatile cellular signaling molecule that can form polymers of eight different linkages, and individual linkage types have been associated with distinct cellular functions. Though little is currently known about Lys11-linked ubiquitin chains, recent data indicate that they may be as abundant as Lys48 linkages and may be involved in vital cellular processes. Here we report the generation of Lys11-linked polyubiquitin in vitro, for which the Lys11-specific E2 enzyme UBE2S was fused to a ubiquitin binding domain. Crystallographic and NMR analyses of Lys11-linked diubiquitin reveal that Lys11-linked chains adopt compact conformations in which Ile44 is solvent exposed. Furthermore, we identify the OTU family deubiquitinase Cezanne as the first deubiquitinase with Lys11-linkage preference. Our data highlight the intrinsic specificity of the ubiquitin system that extends to Lys11-linked chains and emphasize that differentially linked polyubiquitin chains must be regarded as independent post-translational modifications.

MeSH terms

  • Crystallography, X-Ray
  • Endopeptidases / metabolism*
  • Humans
  • Hydrolysis
  • Lysine / metabolism*
  • Magnetic Resonance Spectroscopy
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Reproducibility of Results
  • Solutions
  • Substrate Specificity
  • Ubiquitin / chemistry*
  • Ubiquitin / metabolism*
  • Ubiquitin-Conjugating Enzymes / chemistry
  • Ubiquitin-Conjugating Enzymes / metabolism
  • Ubiquitination


  • Solutions
  • Ubiquitin
  • Ube2S protein, human
  • Ubiquitin-Conjugating Enzymes
  • Endopeptidases
  • OTUD7B protein, human
  • Lysine

Associated data

  • PDB/2XEW