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- PDB-8xpu: Overall structure of the LAT1-4F2hc bound with JPH203 -

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Basic information

Entry
Database: PDB / ID: 8xpu
TitleOverall structure of the LAT1-4F2hc bound with JPH203
Components
  • Isoform 5 of Amino acid transporter heavy chain SLC3A2
  • Large neutral amino acids transporter small subunit 1
KeywordsTRANSPORT PROTEIN / Transporter / SLC family / inhibitor
Function / homology
Function and homology information


L-tryptophan transmembrane transporter activity / alanine transport / L-tryptophan transmembrane transport / positive regulation of L-leucine import across plasma membrane / cellular response to L-arginine / thyroid hormone transmembrane transporter activity / neutral L-amino acid secondary active transmembrane transporter activity / amino acid import across plasma membrane / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / methionine transport ...L-tryptophan transmembrane transporter activity / alanine transport / L-tryptophan transmembrane transport / positive regulation of L-leucine import across plasma membrane / cellular response to L-arginine / thyroid hormone transmembrane transporter activity / neutral L-amino acid secondary active transmembrane transporter activity / amino acid import across plasma membrane / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / methionine transport / tyrosine transport / L-histidine transport / apical pole of neuron / aromatic amino acid transmembrane transporter activity / amino acid transport complex / L-leucine import across plasma membrane / L-alanine transmembrane transporter activity / isoleucine transport / L-alanine import across plasma membrane / L-amino acid transmembrane transporter activity / phenylalanine transport / valine transport / amino acid transmembrane transport / L-leucine transmembrane transporter activity / calcium:sodium antiporter activity / L-leucine transport / thyroid hormone transport / proline transport / positive regulation of cytokine production involved in immune response / negative regulation of vascular associated smooth muscle cell apoptotic process / neutral amino acid transport / amino acid transmembrane transporter activity / external side of apical plasma membrane / Amino acid transport across the plasma membrane / neutral L-amino acid transmembrane transporter activity / Tryptophan catabolism / exogenous protein binding / xenobiotic transport / anchoring junction / response to muscle activity / antiporter activity / Basigin interactions / microvillus membrane / amino acid transport / positive regulation of interleukin-4 production / response to exogenous dsRNA / positive regulation of interleukin-17 production / positive regulation of glial cell proliferation / tryptophan transport / transport across blood-brain barrier / response to hyperoxia / cellular response to glucose starvation / basal plasma membrane / liver regeneration / negative regulation of autophagy / positive regulation of type II interferon production / peptide antigen binding / calcium ion transport / double-stranded RNA binding / virus receptor activity / melanosome / basolateral plasma membrane / cellular response to lipopolysaccharide / carbohydrate metabolic process / cadherin binding / apical plasma membrane / symbiont entry into host cell / protein heterodimerization activity / lysosomal membrane / negative regulation of gene expression / intracellular membrane-bounded organelle / synapse / cell surface / protein homodimerization activity / RNA binding / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytosol
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
: / Amino acid transporter heavy chain SLC3A2 / Large neutral amino acids transporter small subunit 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsHu, Z. / Yan, R.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32371267 China
CitationJournal: Cell Discov / Year: 2024
Title: Structural basis for the inhibition mechanism of LAT1-4F2hc complex by JPH203.
Authors: Ziwei Hu / Renhong Yan /
History
DepositionJan 4, 2024Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Jul 17, 2024Provider: repository / Type: Initial release
Revision 1.1Jul 24, 2024Group: Data collection / Category: em_admin / em_imaging
Item: _em_admin.last_update / _em_imaging.calibrated_defocus_max ..._em_admin.last_update / _em_imaging.calibrated_defocus_max / _em_imaging.calibrated_defocus_min / _em_imaging.nominal_defocus_max / _em_imaging.nominal_defocus_min
Revision 1.2Jul 31, 2024Group: Data collection / Structure summary / Category: audit_author / em_admin / em_author_list
Item: _audit_author.name / _em_admin.last_update / _em_author_list.author

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Isoform 5 of Amino acid transporter heavy chain SLC3A2
B: Large neutral amino acids transporter small subunit 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)129,5187
Polymers127,3482
Non-polymers2,1705
Water00
1


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

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Components

#1: Protein Isoform 5 of Amino acid transporter heavy chain SLC3A2 / 4F2 cell-surface antigen heavy chain / 4F2hc / 4F2 heavy chain antigen / Lymphocyte activation ...4F2 cell-surface antigen heavy chain / 4F2hc / 4F2 heavy chain antigen / Lymphocyte activation antigen 4F2 large subunit / Solute carrier family 3 member 2


Mass: 70160.828 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SLC3A2, MDU1 / Cell line (production host): HEK293F / Production host: Homo sapiens (human) / References: UniProt: P08195
#2: Protein Large neutral amino acids transporter small subunit 1 / 4F2 light chain / 4F2 LC / 4F2LC / CD98 light chain / Integral membrane protein E16 / E16 / L-type ...4F2 light chain / 4F2 LC / 4F2LC / CD98 light chain / Integral membrane protein E16 / E16 / L-type amino acid transporter 1 / hLAT1 / Solute carrier family 7 member 5 / y+ system cationic amino acid transporter


Mass: 57186.895 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SLC7A5, CD98LC, LAT1, MPE16 / Cell line (production host): HEK293F / Production host: Homo sapiens (human) / References: UniProt: Q01650
#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-VRW / (2~{S})-2-azanyl-3-[4-[(5-azanyl-2-phenyl-1,3-benzoxazol-7-yl)methoxy]-3,5-bis(chloranyl)phenyl]propanoic acid / JPH203 / KYT-0353


Mass: 472.321 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H19Cl2N3O4
Has ligand of interestN

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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: LAT1-4F2hc complex with JPH203 / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT
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

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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 magnification: 105000 X / Nominal defocus max: 1800 nm / Nominal defocus min: 1400 nm / Calibrated defocus min: 1400 nm / Calibrated defocus max: 1800 nm / C2 aperture diameter: 70 µm / Alignment procedure: BASIC
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 1.5625 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 2609
Image scansWidth: 5760 / Height: 4092

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 362237 / Symmetry type: POINT

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