2F4O

The Mouse PNGase-HR23 Complex Reveals a Complete Remodulation of the Protein-Protein Interface Compared to its Yeast Orthologs

Summary for 2F4O

• Entry DOI: 10.2210/pdb2f4o/pdb
• Related: 2F4M
• Related PRD ID: PRD_000338
• Descriptor: peptide N-glycanase, XP-C repair complementing complex 58 kDa protein, PHQ-VAL-ALA-ASP-CF0, ... (6 entities in total)
• Functional Keywords: glycoproteins, ubiquitin-dependent protein degradation, nucleotide excision repair, peptide:n-glycanase, transglutaminase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Mus musculus (house mouse); More
• Cellular location: Nucleus : P54728
• Total number of polymer chains: 3
• Total formula weight: 42690.07

Authors

Zhao, G.,Zhou, X.,Wang, L.,Kisker, C.,Lennarz, W.J.,Schindelin, H. (deposition date: 2005-11-23, release date: 2006-03-07, Last modification date: 2024-11-13)

Primary citation

Zhao, G.,Zhou, X.,Wang, L.,Li, G.,Kisker, C.,Lennarz, W.J.,Schindelin, H.
Structure of the mouse peptide N-glycanase-HR23 complex suggests co-evolution of the endoplasmic reticulum-associated degradation and DNA repair pathways.
J.Biol.Chem., 281:13751-13761, 2006

PubMed Abstract: Peptide N-glycanase removes N-linked oligosaccharides from misfolded glycoproteins as part of the endoplasmic reticulum-associated degradation pathway. This process involves the formation of a tight complex of peptide N-glycanase with Rad23 in yeast and the orthologous HR23 proteins in mammals. In addition to its function in endoplasmic reticulum-associated degradation, HR23 is also involved in DNA repair, where it plays an important role in damage recognition in complex with the xeroderma pigmentosum group C protein. To characterize the dual role of HR23, we have determined the high resolution crystal structure of the mouse peptide N-glycanase catalytic core in complex with the xeroderma pigmentosum group C binding domain from HR23B. Peptide N-glycanase features a large cleft between its catalytic cysteine protease core and zinc binding domain. Opposite the zinc binding domain is the HR23B-interacting region, and surprisingly, the complex interface is fundamentally different from the orthologous yeast peptide N-glycanase-Rad23 complex. Different regions on both proteins are involved in complex formation, revealing an amazing degree of divergence in the interaction between two highly homologous proteins. Furthermore, the mouse peptide N-glycanase-HR23B complex mimics the interaction between xeroderma pigmentosum group C and HR23B, thereby providing a first structural model of how the two proteins interact within the nucleotide excision repair cascade in higher eukaryotes. The different interaction interfaces of the xeroderma pigmentosum group C binding domains in yeast and mammals suggest a co-evolution of the endoplasmic reticulum-associated degradation and DNA repair pathways.

PubMed: 16500903
DOI: 10.1074/jbc.M600137200

Experimental method

X-RAY DIFFRACTION (2.26 Å)