5V6P

CryoEM structure of the ERAD-associated E3 ubiquitin-protein ligase HRD1


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.10 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Cryo-EM structure of the protein-conducting ERAD channel Hrd1 in complex with Hrd3.

Schoebel, S.Mi, W.Stein, A.Ovchinnikov, S.Pavlovicz, R.DiMaio, F.Baker, D.Chambers, M.G.Su, H.Li, D.Rapoport, T.A.Liao, M.

(2017) Nature 548: 352-355

  • DOI: https://doi.org/10.1038/nature23314
  • Primary Citation of Related Structures:  
    5V6P, 5V7V

  • PubMed Abstract: 

    Misfolded endoplasmic reticulum proteins are retro-translocated through the membrane into the cytosol, where they are poly-ubiquitinated, extracted from the membrane, and degraded by the proteasome-a pathway termed endoplasmic reticulum-associated protein degradation (ERAD). Proteins with misfolded domains in the endoplasmic reticulum lumen or membrane are discarded through the ERAD-L and ERAD-M pathways, respectively. In Saccharomyces cerevisiae, both pathways require the ubiquitin ligase Hrd1, a multi-spanning membrane protein with a cytosolic RING finger domain. Hrd1 is the crucial membrane component for retro-translocation, but it is unclear whether it forms a protein-conducting channel. Here we present a cryo-electron microscopy structure of S. cerevisiae Hrd1 in complex with its endoplasmic reticulum luminal binding partner, Hrd3. Hrd1 forms a dimer within the membrane with one or two Hrd3 molecules associated at its luminal side. Each Hrd1 molecule has eight transmembrane segments, five of which form an aqueous cavity extending from the cytosol almost to the endoplasmic reticulum lumen, while a segment of the neighbouring Hrd1 molecule forms a lateral seal. The aqueous cavity and lateral gate are reminiscent of features of protein-conducting conduits that facilitate polypeptide movement in the opposite direction-from the cytosol into or across membranes. Our results suggest that Hrd1 forms a retro-translocation channel for the movement of misfolded polypeptides through the endoplasmic reticulum membrane.


  • Organizational Affiliation

    Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ERAD-associated E3 ubiquitin-protein ligase HRD1
A, B
407Saccharomyces cerevisiae S288CMutation(s): 0 
Gene Names: HRD1DER3YOL013C
EC: 2.3.2.27
Membrane Entity: Yes 
UniProt
Find proteins for Q08109 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c))
Explore Q08109 
Go to UniProtKB:  Q08109
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ08109
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.10 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONGeRelion1.0

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR01GM052586

Revision History  (Full details and data files)

  • Version 1.0: 2017-08-16
    Type: Initial release
  • Version 1.1: 2017-08-23
    Changes: Author supporting evidence, Database references
  • Version 1.2: 2017-08-30
    Changes: Database references
  • Version 1.3: 2018-07-18
    Changes: Data collection, Experimental preparation
  • Version 1.4: 2020-01-01
    Changes: Author supporting evidence
  • Version 1.5: 2024-03-13
    Changes: Data collection, Database references