The AAA ATPase p97 links peptide N-glycanase to the endoplasmic reticulum-associated E3 ligase autocrine motility factor receptor.
Mouse peptide N-glycanase (mPNGase) cleaves the N-glycan chain from misfolded glycoproteins and glycopeptides. Previously, several proteins were found to directly interact with mPNGase; among them, both mHR23B and mS4 were found to link mPNGase to the proteasome. In this study, we found that the cytoplasmic protein mp97 participates in the formation of a ternary complex containing mouse autocrine motility factor receptor (mAMFR), mp97, and mPNGase. This assemblage recruits the cytosolic mPNGase close to the endoplasmic reticulum (ER) membrane, where the retrotranslocation of misfolded glycoproteins is thought to occur. In addition to the ER membrane-associated E3 ligase mAMFR, a cytosolic protein mY33K, containing both UBA and UBX domains, was found to also directly interact with mp97. Thus, a complex containing five proteins, mAMFR, mY33K, mp97, mPNGase, and mHR23B, is formed in close proximity to the ER membrane and serves to couple the activities of retrotranslocation, ubiquitination, and deglycosylation and, thereby, route misfolded glycoproteins to the proteasome.
Li
Guangtao
G
Department of Biochemistry and Cell Biology, 450 Life Sciences Building, Stony Brook University, Stony Brook, NY 11794-5215, USA.
Zhao
Gang
G
Zhou
Xiaoke
X
Schindelin
Hermann
H
Lennarz
William J
WJ
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D017124:Conserved Sequence; D003600:Cytosol / Q000201:enzymology; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D060285:Receptors, Autocrine Motility Factor; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
D009687:Nuclear Proteins; D018121:Receptors, Cytokine; C555002:Amfr protein, mouse; D060285:Receptors, Autocrine Motility Factor; D044767:Ubiquitin-Protein Ligases; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D000251:Adenosine Triphosphatases; C404942:p97 ATPase