Journal
CELL
Volume 166, Issue 2, Pages 394-407Publisher
CELL PRESS
DOI: 10.1016/j.cell.2016.05.048
Keywords
-
Categories
Funding
- NIH/NIGMS [R01GM052586]
Ask authors/readers for more resources
Misfolded proteins of the ER are retrotranslocated to the cytosol, where they are polyubiquitinated, extracted from the membrane, and degraded by the proteasome. To investigate how the ER-associated Degradation ( ERAD) machinery can accomplish retrotranslocation of a misfolded luminal protein domain across a lipid bilayer, we have reconstituted retrotranslocation with purified S. cerevisiae proteins, using proteoliposomes containing the multispanning ubiquitin ligase Hrd1. Retrotranslocation of the luminal domain of a membrane-spanning substrate is triggered by autoubiquitination of Hrd1. Substrate ubiquitination is a subsequent event, and the Cdc48 ATPase that completes substrate extraction from the membrane is not required for retrotranslocation. Ubiquitination of lysines in Hrd1's RING-finger domain is required for substrate retrotranslocation in vitro and for ERAD in vivo. Our results suggest that Hrd1 forms a ubiquitin-gated protein-conducting channel.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available