[English] 日本語
Yorodumi
- PDB-9og0: Cryo-EM structure of OS9-SEL1L-HRD1 dimer -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9og0
TitleCryo-EM structure of OS9-SEL1L-HRD1 dimer
Components
  • E3 ubiquitin-protein ligase synoviolin
  • Isoform 2 of Protein OS-9
  • Protein sel-1 homolog 1
KeywordsMEMBRANE PROTEIN / ERAD / SEL1L / OS9 / HRD1
Function / homology
Function and homology information


glycosylation-dependent protein binding / negative regulation of retrograde protein transport, ER to cytosol / protein retention in ER lumen / Hrd1p ubiquitin ligase complex / endoplasmic reticulum mannose trimming / Hedgehog ligand biogenesis / Hrd1p ubiquitin ligase ERAD-L complex / endoplasmic reticulum quality control compartment / ABC-family proteins mediated transport / XBP1(S) activates chaperone genes ...glycosylation-dependent protein binding / negative regulation of retrograde protein transport, ER to cytosol / protein retention in ER lumen / Hrd1p ubiquitin ligase complex / endoplasmic reticulum mannose trimming / Hedgehog ligand biogenesis / Hrd1p ubiquitin ligase ERAD-L complex / endoplasmic reticulum quality control compartment / ABC-family proteins mediated transport / XBP1(S) activates chaperone genes / immature B cell differentiation / Derlin-1 retrotranslocation complex / triglyceride metabolic process / retrograde protein transport, ER to cytosol / ubiquitin-specific protease binding / protein secretion / protein targeting / smooth endoplasmic reticulum / protein K48-linked ubiquitination / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / endoplasmic reticulum unfolded protein response / ERAD pathway / Notch signaling pathway / ER Quality Control Compartment (ERQC) / endomembrane system / response to endoplasmic reticulum stress / Hh mutants are degraded by ERAD / Hedgehog ligand biogenesis / Defective CFTR causes cystic fibrosis / RING-type E3 ubiquitin transferase / ABC-family proteins mediated transport / ubiquitin protein ligase activity / unfolded protein binding / protein-folding chaperone binding / ATPase binding / carbohydrate binding / protease binding / ubiquitin-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / protein stabilization / protein ubiquitination / endoplasmic reticulum lumen / endoplasmic reticulum membrane / endoplasmic reticulum / zinc ion binding / nucleoplasm / membrane
Similarity search - Function
Protein OS9-like domain / Protein OS-9-like / Glucosidase II beta subunit-like protein / : / : / Sel1 repeat / Sel1-like repeat / Sel1-like repeats. / Mannose-6-phosphate receptor binding domain superfamily / MRH domain ...Protein OS9-like domain / Protein OS-9-like / Glucosidase II beta subunit-like protein / : / : / Sel1 repeat / Sel1-like repeat / Sel1-like repeats. / Mannose-6-phosphate receptor binding domain superfamily / MRH domain / MRH domain profile. / Ring finger domain / Fibronectin type II domain / Fibronectin type II domain superfamily / Fibronectin type II domain / Fibronectin type-II collagen-binding domain signature. / Fibronectin type-II collagen-binding domain profile. / Fibronectin type 2 domain / Kringle-like fold / Ring finger / Zinc finger RING-type profile. / Zinc finger, RING-type / Tetratricopeptide-like helical domain superfamily / Zinc finger, RING/FYVE/PHD-type
Similarity search - Domain/homology
Protein OS-9 / E3 ubiquitin-protein ligase synoviolin / Protein sel-1 homolog 1
Similarity search - Component
Biological speciesHomo sapiens (human)
Mus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.64 Å
AuthorsLin, L. / Maldosevic, E. / Jomaa, A. / Qi, L.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)1R35GM130292 United States
CitationJournal: bioRxiv / Year: 2025
Title: Structural basis and pathological implications of the dimeric OS9-SEL1L-HRD1 ERAD Core Complex.
Authors: Liangguang Leo Lin / Emir Maldosevic / Linyao Elina Zhou / Ahmad Jomaa / Ling Qi
Abstract: The SEL1L-HRD1 complex represents the most conserved branch of endoplasmic reticulum (ER)-associated degradation (ERAD), a critical pathway that clears misfolded proteins to maintain ER proteostasis. ...The SEL1L-HRD1 complex represents the most conserved branch of endoplasmic reticulum (ER)-associated degradation (ERAD), a critical pathway that clears misfolded proteins to maintain ER proteostasis. However, the molecular organization and pathogenic mechanisms of mammalian ERAD have remained elusive. Here, we report the first cryo-EM structure of the core mammalian ERAD complex, comprising the ER lectin OS9, SEL1L, and the E3 ubiquitin ligase HRD1. The structure, validated by mutagenesis and crosslinking assays, reveals a dimeric assembly of the core complex in which SEL1L and OS9 form a claw-like configuration in the ER lumen that mediates substrate engagement, while HRD1 dimerizes within the membrane to facilitate substrate translocation. Pathogenic SEL1L mutations at the SEL1L-OS9 (Gly585Asp) and SEL1L-HRD1 (Ser658Pro) interfaces disrupt complex formation and impair ERAD activity. A newly identified disease-associated HRD1 variant (Ala91Asp), located in transmembrane helix 3, impairs HRD1 dimerization and substrate processing, underscoring the functional necessity of this interface and HRD1 dimerization. Finally, the structure also reveals two methionine-rich crevices flanking the HRD1 dimer, suggestive of substrate-conducting channels analogous to those in the ER membrane protein complex (EMC). These findings establish a structural framework for mammalian ERAD and elucidate how mutations destabilizing this machinery contribute to human disease.
SUMMARY: The dimeric structure of the human SEL1L-HRD1 ERAD core complex reveals key architectural and functional principles underlying the recognition and processing of misfolded proteins linked to human disease.
History
DepositionApr 30, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 30, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: E3 ubiquitin-protein ligase synoviolin
B: E3 ubiquitin-protein ligase synoviolin
C: Protein sel-1 homolog 1
D: Protein sel-1 homolog 1
E: Isoform 2 of Protein OS-9
F: Isoform 2 of Protein OS-9


Theoretical massNumber of molelcules
Total (without water)451,0306
Polymers451,0306
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein E3 ubiquitin-protein ligase synoviolin / RING-type E3 ubiquitin transferase synoviolin / Synovial apoptosis inhibitor 1


Mass: 67744.586 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SYVN1, HRD1, KIAA1810 / Production host: Homo sapiens (human)
References: UniProt: Q86TM6, RING-type E3 ubiquitin transferase
#2: Protein Protein sel-1 homolog 1 / Suppressor of lin-12-like protein 1 / Sel-1L


Mass: 88435.148 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Sel1l, Sel1h / Production host: Homo sapiens (human) / References: UniProt: Q9Z2G6
#3: Protein Isoform 2 of Protein OS-9 / Amplified in osteosarcoma 9


Mass: 69335.352 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: OS9 / Production host: Homo sapiens (human) / References: UniProt: Q13438
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: OS9-SEL1L-HRD1 Dimer / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

EM softwareName: PHENIX / Version: 1.20.1_4487: / Category: model refinement
CTF correctionType: NONE
3D reconstructionResolution: 3.64 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 192786 / Symmetry type: POINT
Atomic model buildingProtocol: AB INITIO MODEL
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00218424
ELECTRON MICROSCOPYf_angle_d0.43124904
ELECTRON MICROSCOPYf_dihedral_angle_d10.7856702
ELECTRON MICROSCOPYf_chiral_restr0.0352620
ELECTRON MICROSCOPYf_plane_restr0.0043214

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more