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- PDB-8kdf: Structure of LAT1-CD98hc in complex with JPH203, focused on TMD -

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Basic information

Entry
Database: PDB / ID: 8kdf
TitleStructure of LAT1-CD98hc in complex with JPH203, focused on TMD
Components
  • 4F2 cell-surface antigen heavy chain
  • Large neutral amino acids transporter small subunit 1
KeywordsTRANSPORT PROTEIN / Transporter / Amino acid / Complex / Cancer
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 / apical pole of neuron / amino acid import across plasma membrane / aromatic amino acid transmembrane transporter activity ...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 / apical pole of neuron / amino acid import across plasma membrane / aromatic amino acid transmembrane transporter activity / tyrosine transport / L-histidine transport / amino acid transport complex / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / L-leucine import across plasma membrane / L-alanine transmembrane transporter activity / L-alanine import across plasma membrane / phenylalanine transport / isoleucine transport / methionine transport / valine transport / L-leucine transmembrane transporter activity / L-amino acid transmembrane transporter activity / calcium:sodium antiporter activity / thyroid hormone transport / L-leucine transport / proline transport / positive regulation of cytokine production involved in immune response / amino acid transmembrane transport / negative regulation of vascular associated smooth muscle cell apoptotic process / neutral amino acid transport / amino acid transmembrane transporter activity / Amino acid transport across the plasma membrane / external side of apical plasma membrane / neutral L-amino acid transmembrane transporter activity / Tryptophan catabolism / exogenous protein binding / anchoring junction / antiporter activity / Basigin interactions / xenobiotic transport / microvillus membrane / response to muscle activity / amino acid transport / positive regulation of interleukin-4 production / response to exogenous dsRNA / positive regulation of interleukin-17 production / tryptophan transport / response to hyperoxia / transport across blood-brain barrier / cellular response to glucose starvation / positive regulation of glial cell proliferation / negative regulation of autophagy / basal plasma membrane / liver regeneration / peptide antigen binding / positive regulation of type II interferon production / calcium ion transport / double-stranded RNA binding / melanosome / virus receptor activity / cellular response to lipopolysaccharide / basolateral plasma membrane / 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
CHOLESTEROL / 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine / : / 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: 3.89 Å
AuthorsLee, Y.
Funding support Germany, 1items
OrganizationGrant numberCountry
Max Planck Society Germany
CitationJournal: To Be Published
Title: Structural basis of anticancer drug recognition and amino acid transport by LAT1
Authors: Lee, Y.
History
DepositionAug 9, 2023Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Feb 12, 2025Provider: repository / Type: Initial release

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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: Large neutral amino acids transporter small subunit 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)126,1196
Polymers124,1132
Non-polymers2,0064
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 4F2 cell-surface antigen heavy chain / Glycoprotein / 4F2hc / 4F2 heavy chain antigen / Lymphocyte activation antigen 4F2 large subunit / ...Glycoprotein / 4F2hc / 4F2 heavy chain antigen / Lymphocyte activation antigen 4F2 large subunit / Solute carrier family 3 member 2


Mass: 68069.625 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): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P08195
#2: Protein Large neutral amino acids transporter small subunit 1 / 4F2 light chain / 4F2LC / CD98 light chain / Integral membrane protein E16 / L-type amino acid ...4F2 light chain / 4F2LC / CD98 light chain / Integral membrane protein E16 / L-type amino acid transporter 1 / hLAT1 / Solute carrier family 7 member 5 / y+ system cationic amino acid transporter


Mass: 56043.746 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): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q01650
#3: Chemical ChemComp-CLR / CHOLESTEROL


Mass: 386.654 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C27H46O
#4: Chemical ChemComp-LBN / 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine / (2R)-2-[(9Z)-9-Octadecenoyloxy]-3-(palmitoyloxy)propyl 2-(trimethylammonio)ethyl phosphate


Mass: 760.076 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C42H82NO8P / Comment: phospholipid*YM
#5: Chemical ChemComp-VRW / Nanvuranlat / (2~{S})-2-azanyl-3-[4-[(5-azanyl-2-phenyl-1,3-benzoxazol-7-yl)methoxy]-3,5-bis(chloranyl)phenyl]propanoic acid


Mass: 472.321 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H19Cl2N3O4 / 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: LAT1-CD98hc-Fab170 / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT
Molecular weightValue: 0.173 MDa / Experimental value: NO
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: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 51 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.89 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 137883 / Symmetry type: POINT
RefinementResolution: 3.89→3.89 Å / Cor.coef. Fo:Fc: 0.889 / SU B: 15.379 / SU ML: 0.223 / ESU R: 0.732
Stereochemistry target values: MAXIMUM LIKELIHOOD WITH PHASES
Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT
RfactorNum. reflection% reflection
Rwork0.33861 --
obs0.33861 28042 100 %
Solvent computationSolvent model: PARAMETERS FOR MASK CACLULATION
Displacement parametersBiso mean: 181.836 Å2
Refinement stepCycle: 1 / Total: 4045
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
ELECTRON MICROSCOPYr_bond_refined_d0.010.0114157
ELECTRON MICROSCOPYr_bond_other_d00.0164171
ELECTRON MICROSCOPYr_angle_refined_deg1.891.6245685
ELECTRON MICROSCOPYr_angle_other_deg0.6311.5539569
ELECTRON MICROSCOPYr_dihedral_angle_1_deg6.9925504
ELECTRON MICROSCOPYr_dihedral_angle_2_deg18.6116.520
ELECTRON MICROSCOPYr_dihedral_angle_3_deg14.61610651
ELECTRON MICROSCOPYr_dihedral_angle_4_deg
ELECTRON MICROSCOPYr_chiral_restr0.0880.2685
ELECTRON MICROSCOPYr_gen_planes_refined0.0040.024617
ELECTRON MICROSCOPYr_gen_planes_other0.0010.02933
ELECTRON MICROSCOPYr_nbd_refined
ELECTRON MICROSCOPYr_nbd_other
ELECTRON MICROSCOPYr_nbtor_refined
ELECTRON MICROSCOPYr_nbtor_other
ELECTRON MICROSCOPYr_xyhbond_nbd_refined
ELECTRON MICROSCOPYr_xyhbond_nbd_other
ELECTRON MICROSCOPYr_metal_ion_refined
ELECTRON MICROSCOPYr_metal_ion_other
ELECTRON MICROSCOPYr_symmetry_vdw_refined
ELECTRON MICROSCOPYr_symmetry_vdw_other
ELECTRON MICROSCOPYr_symmetry_hbond_refined
ELECTRON MICROSCOPYr_symmetry_hbond_other
ELECTRON MICROSCOPYr_symmetry_metal_ion_refined
ELECTRON MICROSCOPYr_symmetry_metal_ion_other
ELECTRON MICROSCOPYr_mcbond_it30.05115.242025
ELECTRON MICROSCOPYr_mcbond_other30.05115.2412025
ELECTRON MICROSCOPYr_mcangle_it40.41427.632526
ELECTRON MICROSCOPYr_mcangle_other40.40727.642527
ELECTRON MICROSCOPYr_scbond_it39.14119.6632132
ELECTRON MICROSCOPYr_scbond_other39.13219.6612133
ELECTRON MICROSCOPYr_scangle_it
ELECTRON MICROSCOPYr_scangle_other58.52734.4713160
ELECTRON MICROSCOPYr_long_range_B_refined58.331193.8216702
ELECTRON MICROSCOPYr_long_range_B_other58.329193.8216703
ELECTRON MICROSCOPYr_rigid_bond_restr
ELECTRON MICROSCOPYr_sphericity_free
ELECTRON MICROSCOPYr_sphericity_bonded
LS refinement shellResolution: 3.7→3.796 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0 0 -
Rwork1.629 2096 -
obs--100 %

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