Derlin-1 is a rhomboid pseudoprotease required for the dislocation of misfolded proteins from the endoplasmic reticulum
Abstract/Contents
- Abstract
- The degradation of misfolded secretory proteins is ultimately mediated by the ubiquitin-proteasome system in the cytoplasm, therefore endoplasmic reticulum-associated degradation (ERAD) substrates must be dislocated across the ER membrane through a process driven by the AAA ATPase p97/VCP. Derlins recruit p97/VCP and have been proposed to be part of the dislocation machinery. Here we report that Derlins are inactive members of the rhomboid family of intramembrane proteases and bind p97/VCP through C-terminal SHP boxes. Human Derlin-1 harboring mutations within the rhomboid domain stabilized mutant [alpha]-1 antitrypsin (NHK) at the cytosolic face of the ER membrane without disrupting the p97/VCP interaction. We propose that substrate interaction and p97/VCP recruitment are separate functions that are essential for dislocation and can be assigned respectively to the rhomboid domain and the C terminus of Derlin-1. These data suggest that intramembrane proteolysis and protein dislocation share unexpected mechanistic features.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2011 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Greenblatt, Ethan Joseph |
|---|---|
| Associated with | Stanford University, Biophysics Program. |
| Primary advisor | Kopito, Ron Rieger |
| Thesis advisor | Kopito, Ron Rieger |
| Thesis advisor | Bogyo, Matthew, 1971- |
| Thesis advisor | Elias, Joshua |
| Thesis advisor | Harbury, Pehr |
| Advisor | Bogyo, Matthew, 1971- |
| Advisor | Elias, Joshua |
| Advisor | Harbury, Pehr |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Ethan J. Greenblatt. |
|---|---|
| Note | Submitted to the Program in Biophysics. |
| Thesis | Ph. D. Stanford University 2011 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Ethan Joseph Greenblatt
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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