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- EMDB-63006: Overall structure of the y+LAT2-4F2hc bound with Leu -

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Basic information

Entry
Database: EMDB / ID: EMD-63006
TitleOverall structure of the y+LAT2-4F2hc bound with Leu
Map data
Sample
  • Complex: Overall structure of the y+LAT2-4F2hc bound with Leu
    • Protein or peptide: Y+L amino acid transporter 2
    • Protein or peptide: Amino acid transporter heavy chain SLC3A2
  • Ligand: LEUCINE
KeywordsAmino acid / transporter / complex / MEMBRANE PROTEIN
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
Amino acid transporter heavy chain SLC3A2 / Y+L amino acid transporter 2
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.58 Å
AuthorsYan RH / Dai I / Zhang T
Funding support China, 1 items
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, 2025-
Header (metadata) releaseApr 23, 2025-
Map releaseApr 23, 2025-
UpdateMay 13, 2026-
Current statusMay 13, 2026Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_63006.png

Downloads & links

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Map

FileDownload / File: emd_63006.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.86 Å/pix.
x 256 pix.
= 218.88 Å		0.86 Å/pix.
x 256 pix.
= 218.88 Å		0.86 Å/pix.
x 256 pix.
= 218.88 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.855 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.3
Minimum - Maximum-2.2619119 - 3.1918573
Average (Standard dev.)0.0027523646 (±0.06992061)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 218.88 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_63006_half_map_1.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_63006_half_map_2.map
Projections & Slices
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Sample components

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Entire : Overall structure of the y+LAT2-4F2hc bound with Leu

EntireName: Overall structure of the y+LAT2-4F2hc bound with Leu
Components
  • Complex: Overall structure of the y+LAT2-4F2hc bound with Leu
    • Protein or peptide: Y+L amino acid transporter 2
    • Protein or peptide: Amino acid transporter heavy chain SLC3A2
  • Ligand: LEUCINE

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Supramolecule #1: Overall structure of the y+LAT2-4F2hc bound with Leu

SupramoleculeName: Overall structure of the y+LAT2-4F2hc bound with Leu / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Y+L amino acid transporter 2

MacromoleculeName: Y+L amino acid transporter 2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 58.934102 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DYKDDDDKSG PDEVDASGRM EAREPGRPTP TYHLVPNTSQ SQVEEDVSSP PQRSSETMQL KKEISLLNGV SLVVGNMIGS GIFVSPKGV LVHTASYGMS LIVWAIGGLF SVVGALCYAE LGTTITKSGA SYAYILEAFG GFIAFIRLWV SLLVVEPTGQ A IIAITFAN ...String:
DYKDDDDKSG PDEVDASGRM EAREPGRPTP TYHLVPNTSQ SQVEEDVSSP PQRSSETMQL KKEISLLNGV SLVVGNMIGS GIFVSPKGV LVHTASYGMS LIVWAIGGLF SVVGALCYAE LGTTITKSGA SYAYILEAFG GFIAFIRLWV SLLVVEPTGQ A IIAITFAN YIIQPSFPSC DPPYLACRLL AAACICLLTF VNCAYVKWGT RVQDTFTYAK VVALIAIIVM GLVKLCQGHS EH FQDAFEG SSWDMGNLSL ALYSALFSYS GWDTLNFVTE EIKNPERNLP LAIGISMPIV TLIYILTNVA YYTVLNISDV LSS DAVAVT FADQTFGMFS WTIPIAVALS CFGGLNASIF ASSRLFFVGS REGHLPDLLS MIHIERFTPI PALLFNCTMA LIYL IVEDV FQLINYFSFS YWFFVGLSVV GQLYLRWKEP KRPRPLKLSV FFPIVFCICS VFLVIVPLFT DTINSLIGIG IALSG VPFY FMGVYLPESR RPLFIRNVLA AITRGTQQLC FCVLTELDVA EEKKDERKTD

UniProtKB: Y+L amino acid transporter 2

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Macromolecule #2: Amino acid transporter heavy chain SLC3A2

MacromoleculeName: Amino acid transporter heavy chain SLC3A2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 69.837523 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: HHHHHHHHHH SGRELQPPEA SIAVVSIPRQ LPGSHSEAGV QGLSAGDDSE LGSHCVAQTG LELLASGDPL PSASQNAEMI ETGSDCVTQ AGLQLLASSD PPALASKNAE VTGTMSQDTE VDMKEVELNE LEPEKQPMNA ASGAAMSLAG AEKNGLVKIK V AEDEAEAA ...String:
HHHHHHHHHH SGRELQPPEA SIAVVSIPRQ LPGSHSEAGV QGLSAGDDSE LGSHCVAQTG LELLASGDPL PSASQNAEMI ETGSDCVTQ AGLQLLASSD PPALASKNAE VTGTMSQDTE VDMKEVELNE LEPEKQPMNA ASGAAMSLAG AEKNGLVKIK V AEDEAEAA AAAKFTGLSK EELLKVAGSP GWVRTRWALL LLFWLGWLGM LAGAVVIIVR APRCRELPAQ KWWHTGALYR IG DLQAFQG HGAGNLAGLK GRLDYLSSLK VKGLVLGPIH KNQKDDVAQT DLLQIDPNFG SKEDFDSLLQ SAKKKSIRVI LDL TPNYRG ENSWFSTQVD TVATKVKDAL EFWLQAGVDG FQVRDIENLK DASSFLAEWQ NITKGFSEDR LLIAGTNSSD LQQI LSLLE SNKDLLLTSS YLSDSGSTGE HTKSLVTQYL NATGNRWCSW SLSQARLLTS FLPAQLLRLY QLMLFTLPGT PVFSY GDEI GLDAAALPGQ PMEAPVMLWD ESSFPDIPGA VSANMTVKGQ SEDPGSLLSL FRRLSDQRSK ERSLLHGDFH AFSAGP GLF SYIRHWDQNE RFLVVLNFGD VGLSAGLQAS DLPASASLPA KADLLLSTQP GREEGSPLEL ERLKLEPHEG LLLRFPY AA TGA

UniProtKB: Amino acid transporter heavy chain SLC3A2

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Macromolecule #3: LEUCINE

MacromoleculeName: LEUCINE / type: ligand / ID: 3 / Number of copies: 1 / Formula: LEU
Molecular weightTheoretical: 131.173 Da
Chemical component information

ChemComp-LEU:
LEUCINE

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 5.0 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.58 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 370341
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER

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