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- PDB-9ldr: Overall structure of the y+LAT2-4F2hc bound with Leu -

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Basic information

Entry
Database: PDB / ID: 9ldr
TitleOverall structure of the y+LAT2-4F2hc bound with Leu
Components
  • Amino acid transporter heavy chain SLC3A2
  • Y+L amino acid transporter 2
KeywordsMEMBRANE PROTEIN / Amino acid / transporter / complex
Function / homology
Function and homology information


L-lysine:L-arginine antiporter activity / ornithine transport / basic amino acid transmembrane transporter activity / L-arginine transmembrane transport / L-arginine transmembrane transporter activity / glycine betaine transport / apical pole of neuron / tyrosine transport / L-histidine transport / amino acid transport complex ...L-lysine:L-arginine antiporter activity / ornithine transport / basic amino acid transmembrane transporter activity / L-arginine transmembrane transport / L-arginine transmembrane transporter activity / glycine betaine transport / 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 amino acid transport by SLC7A7 causes lysinuric protein intolerance (LPI) / aromatic amino acid transmembrane transporter activity / phenylalanine transport / methionine transport / valine transport / L-leucine transmembrane transporter activity / isoleucine transport / amino acid transmembrane transport / L-amino acid transmembrane transporter activity / L-leucine transport / proline transport / thyroid hormone transport / neutral amino acid transport / neutral L-amino acid transmembrane transporter activity / Tryptophan catabolism / exogenous protein binding / Amino acid transport across the plasma membrane / anchoring junction / amino acid transmembrane transporter activity / arginine binding / Basigin interactions / response to exogenous dsRNA / amino acid transport / tryptophan transport / nitric oxide biosynthetic process / basal plasma membrane / calcium ion transport / melanosome / double-stranded RNA binding / virus receptor activity / carbohydrate metabolic process / basolateral plasma membrane / apical plasma membrane / cadherin binding / protein heterodimerization activity / lysosomal membrane / symbiont entry into host cell / synapse / cell surface / protein homodimerization activity / RNA binding / extracellular exosome / nucleoplasm / membrane / plasma membrane
Similarity search - Function
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
LEUCINE / Amino acid transporter heavy chain SLC3A2 / Y+L amino acid transporter 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.58 Å
AuthorsYan, R.H. / Dai, I. / Zhang, T.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Structure / Year: 2025
Title: Structural insights into the human system yL amino acid transporter complex.
Authors: Lu Dai / Kangtai Xu / Ting Zhang / Xiaoting Wang / Qian Zeng / Hao Liang / Chenye Xu / Liuqing Yang / Zilong Wang / Renhong Yan /
Abstract: System yL facilitates the sodium-independent transport of cationic and sodium-dependent transport of neutral amino acids via heteromeric amino acid transporters. System yL consists of either SLC7A6 ...System yL facilitates the sodium-independent transport of cationic and sodium-dependent transport of neutral amino acids via heteromeric amino acid transporters. System yL consists of either SLC7A6 (yLAT2) or SLC7A7 (yLAT1) and 4F2hc (SLC3A2). The yLAT2-4F2hc complex mediates the exchange of -lysine (Lys), -arginine (Arg), -leucine (Leu), and -glutamine (Gln) and is important for the glutamate-glutamine cycle and ammonia clearance. c-Myc-driven upregulation of yLAT2 in cancer enhances amino acid uptake and mTORC1 activation, promoting tumor growth. Its transport mechanism has remained unclear. Here, we determined the cryoelectron microscopic (cryo-EM) structures of the yLAT2-4F2hc complex bound to either Arg or Leu at 3.60 Å and 3.58 Å resolution, respectively, revealing an outward-open conformation. Our structural analysis highlights conformational changes during transport, and functional assays validate critical residues involved in substrate binding and transport. These findings elucidate the molecular mechanism of the system yL and provide a foundation for developing targeted therapies against yLAT2.
History
DepositionJan 6, 2025Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Apr 23, 2025Provider: repository / Type: Initial release
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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Y+L amino acid transporter 2
B: Amino acid transporter heavy chain SLC3A2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)128,9033
Polymers128,7722
Non-polymers1311
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

#1: Protein Y+L amino acid transporter 2 / Cationic amino acid transporter / y+ system / Solute carrier family 7 member 6 / y(+)L-type amino ...Cationic amino acid transporter / y+ system / Solute carrier family 7 member 6 / y(+)L-type amino acid transporter 2 / Y+LAT2 / y+LAT-2


Mass: 58934.102 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SLC7A6, KIAA0245 / Production host: Homo sapiens (human) / References: UniProt: Q92536
#2: Protein 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: 69837.523 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SLC3A2, MDU1 / Production host: Homo sapiens (human) / References: UniProt: P08195
#3: Chemical ChemComp-LEU / LEUCINE


Type: L-peptide linking / Mass: 131.173 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C6H13NO2
Has ligand of interestN
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 the y+LAT2-4F2hc bound with Leu / 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: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 5000 nm / Nominal defocus min: 1200 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM softwareName: PHENIX / Version: 1.17.1_3660 / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.58 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 370341 / Symmetry type: POINT
RefinementStereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0067456
ELECTRON MICROSCOPYf_angle_d0.70410143
ELECTRON MICROSCOPYf_dihedral_angle_d14.984999
ELECTRON MICROSCOPYf_chiral_restr0.0441163
ELECTRON MICROSCOPYf_plane_restr0.0051274

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