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- PDB-7epz: Overall structure of Erastin-bound xCT-4F2hc complex -

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Basic information

Entry
Database: PDB / ID: 7epz
TitleOverall structure of Erastin-bound xCT-4F2hc complex
Components
  • 4F2 cell-surface antigen heavy chain
  • Cystine/glutamate transporter
KeywordsMEMBRANE PROTEIN
Function / homology
Function and homology information


cystine:glutamate antiporter activity / regulation of neutrophil apoptotic process / L-kynurenine transmembrane transport / L-kynurenine transmembrane transporter activity / regulation of cysteine metabolic process / regulation of glutathione biosynthetic process / regulation of glutamate metabolic process / regulation of melanin biosynthetic process / regulation of AMPA glutamate receptor clustering / L-cystine transport ...cystine:glutamate antiporter activity / regulation of neutrophil apoptotic process / L-kynurenine transmembrane transport / L-kynurenine transmembrane transporter activity / regulation of cysteine metabolic process / regulation of glutathione biosynthetic process / regulation of glutamate metabolic process / regulation of melanin biosynthetic process / regulation of AMPA glutamate receptor clustering / L-cystine transport / dipeptide import across plasma membrane / apical pole of neuron / tyrosine transport / L-histidine transport / amino acid transport complex / L-leucine import across plasma membrane / L-alanine transmembrane transporter activity / L-alanine import across plasma membrane / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / aromatic amino acid transmembrane transporter activity / phenylalanine transport / methionine transport / L-leucine transmembrane transporter activity / amino acid transmembrane transport / isoleucine transport / valine transport / regulation of protein transport / proline transport / L-amino acid transmembrane transporter activity / L-leucine transport / L-glutamate transmembrane transport / thyroid hormone transport / glutathione transmembrane transport / regulation of cellular response to oxidative stress / intracellular glutamate homeostasis / ventricular system development / neutral L-amino acid transmembrane transporter activity / L-glutamate import across plasma membrane / striatum development / Tryptophan catabolism / Amino acid transport across the plasma membrane / exogenous protein binding / limb development / anchoring junction / response to redox state / Basigin interactions / NFE2L2 regulating anti-oxidant/detoxification enzymes / lung alveolus development / astrocyte projection / negative regulation of ferroptosis / microvillus membrane / regulation of synapse organization / response to exogenous dsRNA / adult behavior / amino acid transport / tryptophan transport / glutathione metabolic process / basal plasma membrane / brush border membrane / visual learning / modulation of chemical synaptic transmission / platelet aggregation / response to toxic substance / apical part of cell / calcium ion transport / melanosome / regulation of cell population proliferation / double-stranded RNA binding / virus receptor activity / cellular response to oxidative stress / basolateral plasma membrane / carbohydrate metabolic process / apical plasma membrane / cadherin binding / protein heterodimerization activity / lysosomal membrane / synapse / symbiont entry into host cell / cell surface / protein homodimerization activity / RNA binding / extracellular exosome / nucleoplasm / membrane / plasma membrane
Similarity search - Function
L-type amino acid transporter / Solute carrier family 3 member 2, N-terminal domain / 4F2 cell-surface antigen heavy chain / Solute carrier family 3 member 2 N-terminus / : / Amino acid/polyamine transporter I / Amino acid permease / Alpha amylase, catalytic domain / Glycosyl hydrolase, family 13, catalytic domain / Alpha-amylase domain ...L-type amino acid transporter / Solute carrier family 3 member 2, N-terminal domain / 4F2 cell-surface antigen heavy chain / Solute carrier family 3 member 2 N-terminus / : / Amino acid/polyamine transporter I / Amino acid permease / Alpha amylase, catalytic domain / Glycosyl hydrolase, family 13, catalytic domain / Alpha-amylase domain / Glycosyl hydrolase, all-beta / Glycoside hydrolase superfamily
Similarity search - Domain/homology
Chem-J9O / 1,2-DISTEAROYL-SN-GLYCERO-3-PHOSPHATE / Amino acid transporter heavy chain SLC3A2 / Cystine/glutamate transporter
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsYan, R.H. / Li, Y.N. / Zhang, Y.Y. / Chi, X.M. / Zhou, Q.
Funding support China, 3items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)31971123 China
National Natural Science Foundation of China (NSFC)81920108015 China
National Natural Science Foundation of China (NSFC)31930059 China
CitationJournal: Cell Res / Year: 2022
Title: The structure of erastin-bound xCT-4F2hc complex reveals molecular mechanisms underlying erastin-induced ferroptosis.
Authors: Renhong Yan / Enjun Xie / Yaning Li / Jin Li / Yuanyuan Zhang / Ximin Chi / Xueping Hu / Lei Xu / Tingjun Hou / Brent R Stockwell / Junxia Min / Qiang Zhou / Fudi Wang /
History
DepositionApr 28, 2021Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Apr 6, 2022Provider: repository / Type: Initial release
Revision 1.1Apr 13, 2022Group: Database references / Category: citation / citation_author
Item: _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name
Revision 2.0May 25, 2022Group: Atomic model / Author supporting evidence ...Atomic model / Author supporting evidence / Data collection / Derived calculations / Non-polymer description / Source and taxonomy / Structure summary
Category: atom_site / chem_comp ...atom_site / chem_comp / em_imaging / em_software / entity / entity_src_gen / pdbx_contact_author / pdbx_entity_instance_feature / pdbx_entity_nonpoly / pdbx_nonpoly_scheme / pdbx_struct_assembly_prop
Item: _atom_site.Cartn_x / _atom_site.Cartn_y ..._atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _atom_site.auth_atom_id / _atom_site.auth_comp_id / _atom_site.label_atom_id / _atom_site.label_comp_id / _atom_site.type_symbol / _chem_comp.formula / _chem_comp.formula_weight / _chem_comp.id / _chem_comp.mon_nstd_flag / _chem_comp.name / _chem_comp.pdbx_synonyms / _chem_comp.type / _em_imaging.nominal_defocus_max / _em_imaging.nominal_defocus_min / _em_software.category / _em_software.fitting_id / _em_software.imaging_id / _entity.formula_weight / _entity.pdbx_description / _entity_src_gen.gene_src_common_name / _pdbx_entity_instance_feature.auth_comp_id / _pdbx_entity_instance_feature.comp_id / _pdbx_entity_nonpoly.comp_id / _pdbx_entity_nonpoly.name / _pdbx_nonpoly_scheme.mon_id / _pdbx_nonpoly_scheme.pdb_mon_id
Description: Model completeness / Provider: author / Type: Coordinate replacement
Revision 2.1Jul 13, 2022Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 2.2Oct 30, 2024Group: Data collection / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update / _pdbx_entry_details.has_protein_modification

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: 4F2 cell-surface antigen heavy chain
B: Cystine/glutamate transporter
hetero molecules


Theoretical massNumber of molelcules
Total (without water)131,4239
Polymers127,7712
Non-polymers3,6537
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: microscopy
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein 4F2 cell-surface antigen heavy chain / 4F2hc / Solute carrier family 3 (Activators of dibasic and neutral amino acid transport) / member 2 ...4F2hc / Solute carrier family 3 (Activators of dibasic and neutral amino acid transport) / member 2 / isoform CRA_a


Mass: 70160.828 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SLC3A2, hCG_2016598 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: J3KPF3
#2: Protein Cystine/glutamate transporter / Amino acid transport system xc- / Calcium channel blocker resistance protein CCBR1 / Solute carrier ...Amino acid transport system xc- / Calcium channel blocker resistance protein CCBR1 / Solute carrier family 7 member 11 / xCT


Mass: 57609.777 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SLC7A11 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q9UPY5
#3: Polysaccharide
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}LINUCSPDB-CARE
#4: Chemical ChemComp-J9O / 2-[(1S)-1-[4-[2-(4-chloranylphenoxy)ethanoyl]piperazin-1-yl]ethyl]-3-(2-ethoxyphenyl)quinazolin-4-one


Mass: 547.045 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C30H31ClN4O4 / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical ChemComp-PX8 / 1,2-DISTEAROYL-SN-GLYCERO-3-PHOSPHATE


Mass: 703.990 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C39H76O8P / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

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

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Sample preparation

ComponentName: Overall structure of Erastin-bound xCT-4F2hc complex / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 1200 nm / Alignment procedure: COMA FREE
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

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Processing

EM softwareName: RELION / Version: 3.0.6 / Category: 3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 114524 / Symmetry type: POINT

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