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- EMDB-38775: Structure of y+LAT1 bound with Lys -

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Basic information

Entry
Database: EMDB / ID: EMD-38775
TitleStructure of y+LAT1 bound with Lys
Map data
Sample
  • Complex: Structure of the y+LAT1 bound with Lys
    • Protein or peptide: Y+L amino acid transporter 1
  • Ligand: LYSINE
Keywordscomplex / membrane protein / amino acid
Function / homology
Function and homology information


basic amino acid transmembrane transport / L-arginine transmembrane transporter activity / basic amino acid transmembrane transporter activity / L-arginine transmembrane transport / regulation of arginine metabolic process / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / L-amino acid transmembrane transporter activity / L-leucine transport / amino acid transmembrane transport / Amino acid transport across the plasma membrane ...basic amino acid transmembrane transport / L-arginine transmembrane transporter activity / basic amino acid transmembrane transporter activity / L-arginine transmembrane transport / regulation of arginine metabolic process / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / L-amino acid transmembrane transporter activity / L-leucine transport / amino acid transmembrane transport / Amino acid transport across the plasma membrane / Basigin interactions / basolateral plasma membrane / plasma membrane
Similarity search - Function
: / Amino acid/polyamine transporter I / Amino acid permease
Similarity search - Domain/homology
Y+L amino acid transporter 1
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.33 Å
AuthorsYan RH / Dai L / Zhang T
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Sci Adv / Year: 2025
Title: Structural basis for the substrate recognition and transport mechanism of the human yLAT1-4F2hc transporter complex.
Authors: Lu Dai / Qian Zeng / Ting Zhang / Yuanyuan Zhang / Yi Shi / Yaning Li / Kangtai Xu / Jing Huang / Zilong Wang / Qiang Zhou / Renhong Yan /
Abstract: Heteromeric amino acid transporters (HATs), including yLAT1-4F2hc complex, are responsible for transporting amino acids across membranes, and mutations in yLAT1 cause lysinuric protein intolerance ...Heteromeric amino acid transporters (HATs), including yLAT1-4F2hc complex, are responsible for transporting amino acids across membranes, and mutations in yLAT1 cause lysinuric protein intolerance (LPI), a hereditary disorder characterized by defective cationic amino acid transport. The relationship between LPI and specific mutations in yLAT1 has yet to be fully understood. In this study, we characterized the function of yLAT1-4F2hc complex in mammalian cells and determined the cryo-EM structures of the human yLAT1-4F2hc complex in two distinct conformations: the apo state in an inward-open conformation and the native substrate-bound state in an outward-open conformation. Structural analysis suggests that Asp in yLAT1 plays a crucial role in coordination with sodium ion and substrate selectivity. Molecular dynamic (MD) simulations further revealed the different transport mechanism of cationic amino acids and neutral amino acids. These results provide important insights into the mechanisms of the substrate binding and working cycle of HATs.
History
DepositionJan 19, 2024-
Header (metadata) releaseJan 22, 2025-
Map releaseJan 22, 2025-
UpdateApr 2, 2025-
Current statusApr 2, 2025Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_38775.png

Downloads & links

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Map

FileDownload / File: emd_38775.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 256 pix.
= 211.712 Å		0.83 Å/pix.
x 256 pix.
= 211.712 Å		0.83 Å/pix.
x 256 pix.
= 211.712 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.827 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.34
Minimum - Maximum-2.6204338 - 3.3431005
Average (Standard dev.)0.0029686631 (±0.07375694)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 211.712 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_38775_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_38775_half_map_2.map
Projections & Slices
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Sample components

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Entire : Structure of the y+LAT1 bound with Lys

EntireName: Structure of the y+LAT1 bound with Lys
Components
  • Complex: Structure of the y+LAT1 bound with Lys
    • Protein or peptide: Y+L amino acid transporter 1
  • Ligand: LYSINE

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Supramolecule #1: Structure of the y+LAT1 bound with Lys

SupramoleculeName: Structure of the y+LAT1 bound with Lys / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Y+L amino acid transporter 1

MacromoleculeName: Y+L amino acid transporter 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 57.963137 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DYKDDDDKSG PDEVDASGRV DSTEYEVASQ PEVETSPLGD GASPGPEQVK LKKEISLLNG VCLIVGNMIG SGIFVSPKGV LIYSASFGL SLVIWAVGGL FSVFGALCYA ELGTTIKKSG ASYAYILEAF GGFLAFIRLW TSLLIIEPTS QAIIAITFAN Y MVQPLFPS ...String:
DYKDDDDKSG PDEVDASGRV DSTEYEVASQ PEVETSPLGD GASPGPEQVK LKKEISLLNG VCLIVGNMIG SGIFVSPKGV LIYSASFGL SLVIWAVGGL FSVFGALCYA ELGTTIKKSG ASYAYILEAF GGFLAFIRLW TSLLIIEPTS QAIIAITFAN Y MVQPLFPS CFAPYAASRL LAAACICLLT FINCAYVKWG TLVQDIFTYA KVLALIAVIV AGIVRLGQGA STHFENSFEG SS FAVGDIA LALYSALFSY SGWDTLNYVT EEIKNPERNL PLSIGISMPI VTIIYILTNV AYYTVLDMRD ILASDAVAVT FAD QIFGIF NWIIPLSVAL SCFGGLNASI VAASRLFFVG SREGHLPDAI CMIHVERFTP VPSLLFNGIM ALIYLCVEDI FQLI NYYSF SYWFFVGLSI VGQLYLRWKE PDRPRPLKLS VFFPIVFCLC TIFLVAVPLY SDTINSLIGI AIALSGLPFY FLIIR VPEH KRPLYLRRIV GSATRYLQVL CMSVAAEMDL EDGGEMPKQR DPKSN

UniProtKB: Y+L amino acid transporter 1

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Macromolecule #2: LYSINE

MacromoleculeName: LYSINE / type: ligand / ID: 2 / Number of copies: 1 / Formula: LYS
Molecular weightTheoretical: 147.195 Da
Chemical component information

ChemComp-LYS:
LYSINE

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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

MicroscopeFEI TITAN 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

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.33 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 362623
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER

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