2F4O: The Mouse Pngase-hr23 Complex Reveals A Complete Remodulation Of The Protein-protein Interface Compared To Its Yeast Orthologs

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.
PDB ID: 2F4ODownload
MMDB ID: 106084
PDB Deposition Date: 2005/11/23
Updated in MMDB: 2012/12
Experimental Method:
x-ray diffraction
Resolution: 2.26  Å
Source Organism:
Mus musculus
Similar Structures:
Biological Unit for 2F4O: trimeric; determined by author and by software (PISA)
Molecular Components in 2F4O
Label Count Molecule
Proteins (3 molecules)
Peptide N-glycanase(Gene symbol: Ngly1)
Molecule annotation
Xp-c Repair Complementing Complex 58 KDA Protein(Gene symbol: Rad23b)
Molecule annotation
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB