[English] 日本語
Yorodumi
- PDB-9og9: Cryo-EM structure of human full-length XPO1 (unliganded) -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9og9
TitleCryo-EM structure of human full-length XPO1 (unliganded)
ComponentsExportin-1
KeywordsPROTEIN TRANSPORT / nuclear export / HEAT repeat
Function / homology
Function and homology information


cellular response to triglyceride / cellular response to salt / HuR (ELAVL1) binds and stabilizes mRNA / annulate lamellae / regulation of proteasomal ubiquitin-dependent protein catabolic process / nuclear export signal receptor activity / regulation of centrosome duplication / regulation of protein export from nucleus / Rev-mediated nuclear export of HIV RNA / NEP/NS2 Interacts with the Cellular Export Machinery ...cellular response to triglyceride / cellular response to salt / HuR (ELAVL1) binds and stabilizes mRNA / annulate lamellae / regulation of proteasomal ubiquitin-dependent protein catabolic process / nuclear export signal receptor activity / regulation of centrosome duplication / regulation of protein export from nucleus / Rev-mediated nuclear export of HIV RNA / NEP/NS2 Interacts with the Cellular Export Machinery / nucleocytoplasmic transport / Maturation of hRSV A proteins / ribosomal large subunit export from nucleus / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / protein localization to nucleus / mRNA export from nucleus / Cajal body / Cyclin A/B1/B2 associated events during G2/M transition / ribosomal subunit export from nucleus / NPAS4 regulates expression of target genes / ribosomal small subunit export from nucleus / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Transcriptional and post-translational regulation of MITF-M expression and activity / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / protein export from nucleus / Resolution of Sister Chromatid Cohesion / Downregulation of TGF-beta receptor signaling / Deactivation of the beta-catenin transactivating complex / Heme signaling / RHO GTPases Activate Formins / MAPK6/MAPK4 signaling / kinetochore / small GTPase binding / Separation of Sister Chromatids / nuclear envelope / ribosome biogenesis / nuclear membrane / DNA-binding transcription factor binding / response to xenobiotic stimulus / ribonucleoprotein complex / protein domain specific binding / intracellular membrane-bounded organelle / nucleolus / negative regulation of transcription by RNA polymerase II / protein-containing complex / RNA binding / nucleoplasm / nucleus / membrane / cytosol / cytoplasm
Similarity search - Function
Exportin-1, repeat 3 / Chromosome region maintenance repeat / Exportin-1, repeat 2 / Chromosome region maintenance or exportin repeat / CRM1 / Exportin repeat 2 / CRM1 / Exportin repeat 3 / CRM1 C terminal / Exportin-1, C-terminal / CRM1 C terminal / Exportin-1/5 ...Exportin-1, repeat 3 / Chromosome region maintenance repeat / Exportin-1, repeat 2 / Chromosome region maintenance or exportin repeat / CRM1 / Exportin repeat 2 / CRM1 / Exportin repeat 3 / CRM1 C terminal / Exportin-1, C-terminal / CRM1 C terminal / Exportin-1/5 / Exportin-1/Importin-beta-like / Exportin 1-like protein / Importin-beta N-terminal domain / Importin-beta N-terminal domain / Importin-beta N-terminal domain profile. / Importin-beta, N-terminal domain / Armadillo-like helical / Armadillo-type fold
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.93 Å
AuthorsWing, C.E. / Fung, H.Y.J. / Chook, Y.M.
Funding support United States, 7items
OrganizationGrant numberCountry
Cancer Prevention and Research Institute of Texas (CPRIT)RP220582 United States
Cancer Prevention and Research Institute of Texas (CPRIT)RP180410 United States
Cancer Prevention and Research Institute of Texas (CPRIT)RP150053 United States
Cancer Prevention and Research Institute of Texas (CPRIT)RP170170 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35GM144137 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)T32GM131963 United States
Welch FoundationI-1532 United States
CitationJournal: bioRxiv / Year: 2025
Title: SINE compounds activate exportin-1 degradation via an allosteric mechanism.
Authors: Casey Elizabeth Wing / Ho Yee Joyce Fung / Bert Kwanten / Tolga Cagatay / Ashley B Niesman / Maarten Jacquemyn / Mehdi Gharghabi / Brecht Permentier / Binita Shakya / Rhituparna Nandi / ...Authors: Casey Elizabeth Wing / Ho Yee Joyce Fung / Bert Kwanten / Tolga Cagatay / Ashley B Niesman / Maarten Jacquemyn / Mehdi Gharghabi / Brecht Permentier / Binita Shakya / Rhituparna Nandi / Joseph M Ready / Trinayan Kashyap / Sharon Shacham / Yosef Landesman / Rosa Lapalombella / Dirk Daelemans / Yuh Min Chook
Abstract: The nuclear export receptor exportin 1 (XPO1/CRM1) is often overexpressed in cancer cells, leading to the mislocalization of numerous cancer-related protein cargoes . Selinexor, a covalent XPO1 ...The nuclear export receptor exportin 1 (XPO1/CRM1) is often overexpressed in cancer cells, leading to the mislocalization of numerous cancer-related protein cargoes . Selinexor, a covalent XPO1 inhibitor, and other Selective Inhibitor of Nuclear Export (SINEs) restore proper nuclear localization by blocking XPO1-cargo binding . SINEs also induce XPO1 degradation via the Cullin-RING E3 ubiquitin ligase (CRL) substrate receptor ASB8 . Here we elucidate the mechanism underlying the high-affinity engagement of CRL5 with SINE-conjugated XPO1. Cryogenic electron microscopy (cryoEM) structures reveal that ASB8 binds to a cryptic site on XPO1, which becomes accessible only upon SINE conjugation. While molecular glue degraders typically interact with both CRL and the substrate , SINEs bind to XPO1 without requiring interaction with ASB8 for efficient XPO1 degradation. Instead, an allosteric mechanism facilitates high affinity XPO1-ASB8 interaction, leading to XPO1 ubiquitination and degradation. ASB8-mediated degradation is also observed upon treatment of the endogenous itaconate derivate 4-octyl itaconate, which suggests a native mechanism that is inadvertently exploited by synthesized XPO1 inhibitors. This allosteric XPO1 degradation mechanism of SINE compounds expands the known modes of targeted protein degradation beyond the well-characterized molecular glue degraders and proteolysis targeting chimeras of CRL4.
History
DepositionApr 30, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 26, 2025Provider: repository / Type: Initial release
Revision 1.0Nov 26, 2025Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Nov 26, 2025Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Nov 26, 2025Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Nov 26, 2025Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Nov 26, 2025Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Nov 26, 2025Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Dec 3, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Exportin-1


Theoretical massNumber of molelcules
Total (without water)123,6621
Polymers123,6621
Non-polymers00
Water00
1


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

-
Components

#1: Protein Exportin-1 / Exp1 / Chromosome region maintenance 1 protein homolog


Mass: 123662.484 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: GS remaining after TEV cleavage / Source: (gene. exp.) Homo sapiens (human) / Gene: XPO1, CRM1 / Plasmid: pGEX4TT3 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: O14980
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: Human full-length unliganded exportin-1 (XPO1) / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Molecular weightValue: 0.123 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Escherichia coli (E. coli) / Strain: BL21(DE3) / Plasmid: pGEX4TT3
Buffer solutionpH: 7.4
Details: 20 mM HEPES pH 7.4, 110 mM KOAc, 2 mM Mg(OAc)2, 2 mM TCEP
SpecimenConc.: 3.4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 377 K

-
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 magnification: 165000 X / Nominal defocus max: 2200 nm / Nominal defocus min: 900 nm
Specimen holderSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 60 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 8568
EM imaging opticsEnergyfilter name: TFS Selectris X / Energyfilter slit width: 10 eV

-
Processing

EM software
IDNameCategory
1cryoSPARCparticle selection
2Topazparticle selection
3SerialEMimage acquisition
5cryoSPARCCTF correction
8UCSF ChimeraXmodel fitting
9ISOLDEmodel fitting
10Cootmodel fitting
12cryoSPARCinitial Euler assignment
13cryoSPARCfinal Euler assignment
14cryoSPARCclassification
15cryoSPARC3D reconstruction
16PHENIXmodel refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 1245354 / Details: blob picking followed by Topaz picking
3D reconstructionResolution: 2.93 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 365756 / Symmetry type: POINT
Atomic model buildingB value: 124.05 / Protocol: OTHER / Space: REAL
Details: Initial model was docked into maps using UCSF ChimeraX then manually built using Isolde and Coot and refined in PHENIX
Atomic model buildingPDB-ID: 3GB8

3gb8


Pdb chain-ID: A / Accession code: 3GB8 / Source name: PDB / Type: experimental model
RefinementCross valid method: NONE
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
Displacement parametersBiso mean: 124.05 Å2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00237472
ELECTRON MICROSCOPYf_angle_d0.464410124
ELECTRON MICROSCOPYf_chiral_restr0.03481164
ELECTRON MICROSCOPYf_plane_restr0.00331293
ELECTRON MICROSCOPYf_dihedral_angle_d3.5521957

+
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