Structural basis of sugar-recognizing ubiquitin ligase

Nat Struct Mol Biol. 2004 Apr;11(4):365-70. doi: 10.1038/nsmb732. Epub 2004 Feb 29.


SCF(Fbs1) is a ubiquitin ligase that functions in the endoplasmic reticulum (ER)-associated degradation pathway. Fbs1/Fbx2, a member of the F-box proteins, recognizes high-mannose oligosaccharides. Efficient binding to an N-glycan requires di-N-acetylchitobiose (chitobiose). Here we report the crystal structures of the sugar-binding domain (SBD) of Fbs1 alone and in complex with chitobiose. The SBD is composed of a ten-stranded antiparallel beta-sandwich. The structure of the SBD-chitobiose complex includes hydrogen bonds between Fbs1 and chitobiose and insertion of the methyl group of chitobiose into a small hydrophobic pocket of Fbs1. Moreover, NMR spectroscopy has demonstrated that the amino acid residues adjoining the chitobiose-binding site interact with the outer branches of the carbohydrate moiety. Considering that the innermost chitobiose moieties in N-glycans are usually involved in intramolecular interactions with the polypeptide moieties, we propose that Fbs1 interacts with the chitobiose in unfolded N-glycoprotein, pointing the protein moiety toward E2 for ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Carbohydrate Conformation
  • Carbohydrate Metabolism*
  • Carbohydrate Sequence
  • Carbohydrates / chemistry
  • Cloning, Molecular
  • Endoplasmic Reticulum / enzymology
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Polysaccharides / chemistry*
  • Polysaccharides / metabolism*
  • Protein Conformation
  • Protein Folding
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Ubiquitin-Protein Ligases / chemistry*
  • Ubiquitin-Protein Ligases / metabolism*


  • Carbohydrates
  • Polysaccharides
  • Recombinant Proteins
  • Ubiquitin-Protein Ligases

Associated data

  • PDB/1UMH
  • PDB/1UMI