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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 / negative regulation of ferroptosis / neutral L-amino acid secondary active transmembrane transporter activity / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / tyrosine transport / L-histidine transport / apical pole of neuron / dipeptide import across plasma membrane / aromatic amino acid transmembrane transporter activity / amino acid transport complex / L-amino acid transmembrane transporter activity / methionine transport / : / L-leucine import across plasma membrane / L-alanine transmembrane transporter activity / isoleucine transport / L-alanine import across plasma membrane / phenylalanine transport / valine transport / L-leucine transmembrane transporter activity / proline transport / amino acid transmembrane transport / regulation of protein transport / calcium:sodium antiporter activity / L-leucine transport / thyroid hormone transport / glutathione transmembrane transport / L-glutamate transmembrane transport / Amino acid transport across the plasma membrane / neutral L-amino acid transmembrane transporter activity / regulation of cellular response to oxidative stress / lens fiber cell differentiation / ventricular system development / intracellular glutamate homeostasis / L-glutamate import across plasma membrane / Tryptophan catabolism / astrocyte projection / striatum development / exogenous protein binding / amino acid transport / anchoring junction / Basigin interactions / limb development / response to redox state / microvillus membrane / NFE2L2 regulating anti-oxidant/detoxification enzymes / adult behavior / regulation of synapse organization / lung alveolus development / response to exogenous dsRNA / tryptophan transport / glutathione metabolic process / basal plasma membrane / response to nicotine / brush border membrane / modulation of chemical synaptic transmission / visual learning / response to organic cyclic compound / response to toxic substance / platelet aggregation / calcium ion transport / melanosome / double-stranded RNA binding / virus receptor activity / apical part of cell / cellular response to oxidative stress / regulation of cell population proliferation / basolateral plasma membrane / carbohydrate metabolic process / cadherin binding / symbiont entry into host cell / apical plasma membrane / protein heterodimerization activity / lysosomal membrane / synapse / 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 / 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

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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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
Water0
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

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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 FIELDBright-field microscopy / 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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