Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

A complex of Htm1 and the oxidoreductase Pdi1 accelerates degradation of misfolded glycoproteins

[img]
Preview
PDF (Original article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB

Item Type:Article
Title:A complex of Htm1 and the oxidoreductase Pdi1 accelerates degradation of misfolded glycoproteins
Creators Name:Pfeiffer, A. and Stephanowitz, H. and Krause, E. and Volkwein, C. and Hirsch, C. and Jarosch, E. and Sommer, T.
Abstract:A quality control system in the endoplasmic reticulum (ER) efficiently discriminates polypeptides that are in the process of productive folding from conformers that are trapped in an aberrant state. Only the latter are transported into the cytoplasm and degraded in a process termed endoplasmic-reticulum-associated protein degradation (ERAD). In the ER, an enzymatic cascade generates a specific N-glycan structure of seven mannosyl and two N-acetylglucosamine residues (Man7GlcNAc2) on misfolded glycoproteins to facilitate their disposal. We show that a complex encompassing the yeast lectin-like protein Htm1 and the oxidoreductase Pdi1 converts Man8GlcNAc2 on glycoproteins into the Man7GlcNAc2 signal. In vitro, the Htm1/Pdi1 complex processes both unfolded and native proteins albeit with a preference for the former. In vivo, elevated expression of HTM1 causes glycan trimming on misfolded and folded proteins, but only degradation of the non-native species is accelerated. Thus, modification with a Man7GlcNAc2 structure does not inevitably commit a protein for ERAD. The function of Htm1 in ERAD relies on its association with Pdi1, which appears to regulate the access to substrates. Our data support a model in which the balanced activities of Pdi1 and Htm1 are crucial determinants for the efficient removal of misfolded secretory glycoproteins.
Keywords:Endoplasmic-Reticulum-Associated Protein Degradation (ERAD), ER Quality Control, Glycoprotein, Protein Degradation, Protein Disulfide Isomerase, Glycan Processing
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:291
Number:23
Page Range:12195-12207
Date:3 June 2016
Official Publication:https://doi.org/10.1074/jbc.M115.703256
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library