The PUB domain functions as a p97 binding module in human peptide N-glycanase

J Biol Chem. 2006 Sep 1;281(35):25502-8. doi: 10.1074/jbc.M601173200. Epub 2006 Jun 28.


The AAA ATPase p97 is a ubiquitin-selective molecular machine involved in multiple cellular processes, including protein degradation through the ubiquitin-proteasome system and homotypic membrane fusion. Specific p97 functions are mediated by a variety of cofactors, among them peptide N-glycanase, an enzyme that removes glycans from misfolded glycoproteins. Here we report the three-dimensional structure of the aminoterminal PUB domain of human peptide N-glycanase. We demonstrate that the PUB domain is a novel p97 binding module interacting with the D1 and/or D2 ATPase domains of p97 and identify an evolutionary conserved surface patch required for p97 binding. Furthermore, we show that the PUB and UBX domains do not bind to p97 in a mutually exclusive manner. Our results suggest that PUB domain-containing proteins constitute a widespread family of diverse p97 cofactors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / chemistry*
  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry*
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / chemistry*
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Ubiquitin / chemistry


  • Nuclear Proteins
  • Ubiquitin
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
  • Adenosine Triphosphatases
  • p97 ATPase