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PMID: 16709668 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

The AAA ATPase p97 links peptide N-glycanase to the endoplasmic reticulum-associated E3 ligase autocrine motility factor receptor.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 103 ·No. 22 ·2006-05-30 ·Pages 8348-53

Li G, Zhao G, Zhou X, Schindelin H, Lennarz WJ

Abstract

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.

MeSH Terms
Adenosine Triphosphatases/chemistry,genetics,metabolism Amino Acid Sequence Animals COS Cells Chlorocebus aethiops Conserved Sequence Cytosol/enzymology Endoplasmic Reticulum/enzymology Mice Molecular Sequence Data Mutation/genetics Nuclear Proteins/chemistry,genetics,metabolism Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase/genetics,metabolism Protein Binding Protein Structure, Quaternary Receptors, Autocrine Motility Factor Receptors, Cytokine/genetics,metabolism Sequence Alignment Two-Hybrid System Techniques Ubiquitin-Protein Ligases/genetics,metabolism
Chemicals
Nuclear Proteins Receptors, Cytokine Amfr protein, mouse Receptors, Autocrine Motility Factor Ubiquitin-Protein Ligases Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Adenosine Triphosphatases p97 ATPase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Li Guangtao
Department of Biochemistry and Cell Biology, 450 Life Sciences Building, Stony Brook University, Stony Brook, NY 11794-5215, USA.
Zhao Gang
Zhou Xiaoke
Schindelin Hermann
Lennarz William J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0602747103
Published
2006-05-30
Epub
2006-00-18
Pages
8348-53
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1482497
Subset
IM
Grants
NIDDK NIH HHS · R01 DK054835 · United States
NIGMS NIH HHS · R01 GM033184 · United States
NIDDK NIH HHS · DK 54835 · United States
NIGMS NIH HHS · GM 33184 · United States
External Links
PubMed source DOI: 10.1073/pnas.0602747103 PMC Full Text View journal details
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