2hpj
Crystal structure of the PUB domain of mouse PNGase
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OverviewOverview
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.
About this StructureAbout this Structure
2HPJ is a Single protein structure of sequence from Mus musculus with GOL as ligand. Active as Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase, with EC number 3.5.1.52 Full crystallographic information is available from OCA.
ReferenceReference
Studies on peptide:N-glycanase-p97 interaction suggest that p97 phosphorylation modulates endoplasmic reticulum-associated degradation., Zhao G, Zhou X, Wang L, Li G, Schindelin H, Lennarz WJ, Proc Natl Acad Sci U S A. 2007 May 22;104(21):8785-90. Epub 2007 May 11. PMID:17496150
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