2HPL

Crystal structure of the mouse p97/PNGase complex

Summary for 2HPL

• Entry DOI: 10.2210/pdb2hpl/pdb
• Related: 2HPJ
• Descriptor: PNGase, C-terminal of mouse p97/VCP (3 entities in total)
• Functional Keywords: pub domain, winged helix, p97, hydrolase
• Biological source: Mus musculus (house mouse); More
• Cellular location: Cytoplasm : Q9JI78
• Total number of polymer chains: 2
• Total formula weight: 11780.33

Authors

Zhao, G.,Zhou, X.,Wang, L.,Li, G.,Lennarz, W.,Schindelin, H. (deposition date: 2006-07-17, release date: 2007-05-29, Last modification date: 2024-02-14)

Primary citation

Zhao, G.,Zhou, X.,Wang, L.,Li, G.,Schindelin, H.,Lennarz, W.J.
Studies on peptide:N-glycanase-p97 interaction suggest that p97 phosphorylation modulates endoplasmic reticulum-associated degradation.
Proc.Natl.Acad.Sci.Usa, 104:8785-8790, 2007

PubMed Abstract: During endoplasmic reticulum-associated degradation, the multifunctional AAA ATPase p97 is part of a protein degradation complex. p97 associates via its N-terminal domain with various cofactors to recruit ubiquitinated substrates. It also interacts with alternative substrate-processing cofactors, such as Ufd2, Ufd3, and peptide:N-glycanase (PNGase) in higher eukaryotes. These cofactors determine different fates of the substrates and they all bind outside of the N-terminal domain of p97. Here, we describe a cofactor-binding motif of p97 contained within the last 10 amino acid residues of the C terminus, which is both necessary and sufficient to mediate interactions of p97 with PNGase and Ufd3. The crystal structure of the N-terminal domain of PNGase in complex with this motif provides detailed insight into the interaction between p97 and its substrate-processing cofactors. Phosphorylation of p97's highly conserved penultimate tyrosine residue, which is the main phosphorylation site during T cell receptor stimulation, completely blocks binding of either PNGase or Ufd3 to p97. This observation suggests that phosphorylation of this residue modulates endoplasmic reticulum-associated protein degradation activity by discharging substrate-processing cofactors.

PubMed: 17496150
DOI: 10.1073/pnas.0702966104

Experimental method

X-RAY DIFFRACTION (1.8 Å)