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OS-9 and GRP94 deliver mutant α1-antitrypsin to the Hrd1?SEL1L ubiquitin ligase complex for ERAD.
- Source :
- Nature Cell Biology; Mar2008, Vol. 10 Issue 3, p272-282, 11p, 7 Black and White Photographs, 3 Diagrams, 2 Charts, 2 Graphs
- Publication Year :
- 2008
-
Abstract
- Terminally misfolded or unassembled proteins in the early secretory pathway are degraded by a ubiquitin- and proteasome-dependent process known as ER-associated degradation (ERAD). How substrates of this pathway are recognized within the ER and delivered to the cytoplasmic ubiquitin-conjugating machinery is unknown. We report here that OS-9 and XTP3-B/Erlectin are ER-resident glycoproteins that bind to ERAD substrates and, through the SEL1L adaptor, to the ER-membrane-embedded ubiquitin ligase Hrd1. Both proteins contain conserved mannose 6-phosphate receptor homology (MRH) domains, which are required for interaction with SEL1L, but not with substrate. OS-9 associates with the ER chaperone GRP94 which, together with Hrd1 and SEL1L, is required for the degradation of an ERAD substrate, mutant α<subscript>1</subscript>-antitrypsin. These data suggest that XTP3-B and OS-9 are components of distinct, partially redundant, quality control surveillance pathways that coordinate protein folding with membrane dislocation and ubiquitin conjugation in mammalian cells. [ABSTRACT FROM AUTHOR]
- Subjects :
- PROTEINS
UBIQUITIN
MANNOSE
HOMOLOGY (Biology)
PHOSPHATES
Subjects
Details
- Language :
- English
- ISSN :
- 14657392
- Volume :
- 10
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Nature Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- 31139561
- Full Text :
- https://doi.org/10.1038/ncb1689