2I74

Crystal structure of mouse Peptide N-Glycanase C-terminal domain in complex with mannopentaose

Summary for 2I74

• Entry DOI: 10.2210/pdb2i74/pdb
• Related: 2G9F 2G9G
• Descriptor: PNGase, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose, ACETATE ION, ... (5 entities in total)
• Functional Keywords: beta-sandwich, hydrolase
• Biological source: Mus musculus (house mouse)
• Cellular location: Cytoplasm : Q9JI78
• Total number of polymer chains: 2
• Total formula weight: 45934.58

Authors

Zhou, X.,Zhao, G.,Wang, L.,Li, G.,Lennarz, W.J.,Schindelin, H. (deposition date: 2006-08-30, release date: 2006-10-24, Last modification date: 2023-08-30)

Primary citation

Zhou, X.,Zhao, G.,Truglio, J.J.,Wang, L.,Li, G.,Lennarz, W.J.,Schindelin, H.
Structural and biochemical studies of the C-terminal domain of mouse peptide-N-glycanase identify it as a mannose-binding module.
Proc.Natl.Acad.Sci.Usa, 103:17214-17219, 2006

PubMed Abstract: The inability of certain N-linked glycoproteins to adopt their native conformation in the endoplasmic reticulum (ER) leads to their retrotranslocation into the cytosol and subsequent degradation by the proteasome. In this pathway the cytosolic peptide-N-glycanase (PNGase) cleaves the N-linked glycan chains off denatured glycoproteins. PNGase is highly conserved in eukaryotes and plays an important role in ER-associated protein degradation. In higher eukaryotes, PNGase has an N-terminal and a C-terminal extension in addition to its central catalytic domain, which is structurally and functionally related to transglutaminases. Although the N-terminal domain of PNGase is involved in protein-protein interactions, the function of the C-terminal domain has not previously been characterized. Here, we describe biophysical, biochemical, and crystallographic studies of the mouse PNGase C-terminal domain, including visualization of a complex between this domain and mannopentaose. These studies demonstrate that the C-terminal domain binds to the mannose moieties of N-linked oligosaccharide chains, and we further show that it enhances the activity of the mouse PNGase core domain, presumably by increasing the affinity of mouse PNGase for the glycan chains of misfolded glycoproteins.

PubMed: 17088551
DOI: 10.1073/pnas.0602954103

Experimental method

X-RAY DIFFRACTION (1.75 Å)