title: The PUB domain functions as a p97 binding module in human peptide N-glycanase.
abstract: 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.
authors.affiliation: Centre for Protein Engineering, Medical Research Council, Hills Road, Cambridge CB2 2QH, United Kingdom.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Allen
authors.forename: Alexander
authors.initials: A
authors.lastname: Buchberger
authors.forename: Mark
authors.initials: M
authors.lastname: Bycroft
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry*; D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry*; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D025801:Ubiquitin / Q000737:chemistry
chemical_list: D009687:Nuclear Proteins; D025801:Ubiquitin; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D000251:Adenosine Triphosphatases; C404942:p97 ATPase