English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex

Wu, X., Siggel, M., Ovchinnikov, S., Mi, W., Svetlov, V., Nudler, E., et al. (2020). Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex. Science, 368(6489): eaaz2449, pp. 385. doi:10.1126/science.aaz2449.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Wu, Xudong1, Author
Siggel, Marc2, Author              
Ovchinnikov, Sergey3, Author
Mi, Wei4, Author
Svetlov, Vladimir5, Author
Nudler, Evgeny5, Author
Liao, Maofu4, Author
Hummer, Gerhard2, 6, Author              
Rapoport, Tom A.1, Author
Affiliations:
1Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, USA, ou_persistent22              
2Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society, ou_2068292              
3Faculty of Arts and Sciences, Center for Systems Biology, Harvard University, Cambridge, USA, ou_persistent22              
4Department of Cell Biology, Harvard Medical School, Boston, USA, ou_persistent22              
5Howard Hughes Medical Institute and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, USA, ou_persistent22              
6Institute of Biophysics, Goethe University Frankfurt, Frankfurt am Main, Germany, ou_persistent22              

Content

show
hide
Free keywords: -
 Abstract: Misfolded luminal endoplasmic reticulum (ER) proteins undergo ER-associated degradation (ERAD-L): They are retrotranslocated into the cytosol, polyubiquitinated, and degraded by the proteasome. ERAD-L is mediated by the Hrd1 complex (composed of Hrd1, Hrd3, Der1, Usa1, and Yos9), but the mechanism of retrotranslocation remains mysterious. Here, we report a structure of the active Hrd1 complex, as determined by cryo-electron microscopy analysis of two subcomplexes. Hrd3 and Yos9 jointly create a luminal binding site that recognizes glycosylated substrates. Hrd1 and the rhomboid-like Der1 protein form two "half-channels" with cytosolic and luminal cavities, respectively, and lateral gates facing one another in a thinned membrane region. These structures, along with crosslinking and molecular dynamics simulation results, suggest how a polypeptide loop of an ERAD-L substrate moves through the ER membrane.

Details

show
hide
Language(s): eng - English
 Dates: 2020-01-182019-08-252020-03-112020-04-24
 Publication Status: Published in print
 Pages: 13
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1126/science.aaz2449
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Science
  Other : Science
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Washington, D.C. : American Association for the Advancement of Science
Pages: - Volume / Issue: 368 (6489) Sequence Number: eaaz2449 Start / End Page: 385 Identifier: ISSN: 0036-8075
CoNE: https://pure.mpg.de/cone/journals/resource/991042748276600_1