Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/119021
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Type: | Journal article |
Title: | Chaperone-mediated Sec61 channel gating during ER import of small precursor proteins overcomes Sec61 inhibitor-reinforced energy barrier |
Author: | Haßdenteufel, S. Johnson, N. Paton, A. Paton, J. High, S. Zimmermann, R. |
Citation: | Cell Reports, 2018; 23(5):1373-1386 |
Publisher: | Elsevier |
Issue Date: | 2018 |
ISSN: | 2211-1247 2211-1247 |
Statement of Responsibility: | Sarah Haßdenteufel, Nicholas Johnson, Adrienne W. Paton, James C. Paton, Stephen High and Richard Zimmermann |
Abstract: | Protein transport into the mammalian endoplasmic reticulum (ER) is mediated by the heterotrimeric Sec61 channel. The signal recognition particle (SRP) and TRC systems and Sec62 have all been characterized as membrane-targeting components for small presecretory proteins, whereas Sec63 and the lumenal chaperone BiP act as auxiliary translocation components. Here, we report the transport requirements of two natural, small presecretory proteins and engineered variants using semipermeabilized human cells after the depletion of specific ER components. Our results suggest that hSnd2, Sec62, and SRP and TRC receptor each provide alternative targeting pathways for short secretory proteins and define rules of engagement for the actions of Sec63 and BiP during their membrane translocation. We find that the Sec62/Sec63 complex plus BiP can facilitate Sec61 channel opening, thereby allowing precursors that have weak signal peptides or other inhibitory features to translocate. A Sec61 inhibitor can mimic the effect of BiP depletion on Sec61 gating, suggesting that they both act at the same essential membrane translocation step. |
Keywords: | Endoplasmic reticulum; protein targeting and translocation; Sec61 channel gating; Sec62; Sec63; BiP; CAM741; signal peptide; mature region; cluster of positive charges |
Rights: | © 2018 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
DOI: | 10.1016/j.celrep.2018.03.122 |
Published version: | http://dx.doi.org/10.1016/j.celrep.2018.03.122 |
Appears in Collections: | Aurora harvest 4 Molecular and Biomedical Science publications |
Files in This Item:
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hdl_119021.pdf | Published version | 3.74 MB | Adobe PDF | View/Open |
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