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- EMDB-63995: The structure of mCAT1 in complex with its substrate ornithine an... -

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Basic information

Entry
Database: EMDB / ID: EMD-63995
TitleThe structure of mCAT1 in complex with its substrate ornithine and the RBD of FrMLV.
Map data
Sample
  • Complex: The structure of mCAT1 in complex with its substrate ornithine and the RBD of FrMLV
    • Protein or peptide: High affinity cationic amino acid transporter 1
    • Protein or peptide: Surface protein
  • Ligand: L-ornithine
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Keywordsreceptor / complex / MEMBRANE PROTEIN
Function / homology
Function and homology information


L-ornithine transmembrane transporter activity / L-lysine transmembrane transporter activity / lysine transport / L-ornithine transmembrane transport / L-histidine import across plasma membrane / Amino acid transport across the plasma membrane / L-arginine transmembrane transport / L-histidine transmembrane transporter activity / L-arginine transmembrane transporter activity / positive regulation of T cell proliferation ...L-ornithine transmembrane transporter activity / L-lysine transmembrane transporter activity / lysine transport / L-ornithine transmembrane transport / L-histidine import across plasma membrane / Amino acid transport across the plasma membrane / L-arginine transmembrane transport / L-histidine transmembrane transporter activity / L-arginine transmembrane transporter activity / positive regulation of T cell proliferation / virus receptor activity / basolateral plasma membrane / apical plasma membrane / fusion of virus membrane with host plasma membrane / viral envelope / symbiont entry into host cell / virion attachment to host cell / host cell plasma membrane / virion membrane / protein-containing complex / metal ion binding / membrane
Similarity search - Function
Cationic amino acid transport permease / Cationic amino acid transporter, C-terminal / C-terminus of AA_permease / F-MuLV receptor-binding / ENV polyprotein (coat polyprotein) / TLV/ENV coat polyprotein / Amino acid/polyamine transporter I / Amino acid permease
Similarity search - Domain/homology
Envelope glycoprotein / High affinity cationic amino acid transporter 1
Similarity search - Component
Biological speciesMus musculus (house mouse) / Friend murine leukemia virus (ISOLATE 57)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.65 Å
AuthorsXia LY / Yang Y / Chen XM
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32371270 China
CitationJournal: Nat Commun / Year: 2025
Title: Structural insights into cationic amino acid transport and viral receptor engagement by CAT1.
Authors: Lingyun Xia / Bingqian Lin / Rongfeng Zou / Yanyan Wu / Jiaying Xu / Yan Pan / Yuan Yuan / Shuo Li / Yang Yang / Xuemin Chen /
Abstract: Cationic amino acid transporter 1 (CAT1) transports cationic amino acids and plays pivotal roles in cancer proliferation, immune modulation, and nitric oxide metabolism. It also serves as the ...Cationic amino acid transporter 1 (CAT1) transports cationic amino acids and plays pivotal roles in cancer proliferation, immune modulation, and nitric oxide metabolism. It also serves as the specific cellular receptor for certain murine leukemia viruses. Here, we report the cryo-electron microscopy (cryo-EM) structure of mammalian CAT1 in complex with its substrate ornithine and the receptor-binding domain (RBD) of Friend murine leukemia virus (FrMLV). CAT1 specifically recognizes the side-chain amino group of ornithine via residue S347 on transmembrane helix 8 (TM8), capturing the transporter in an inward-facing occluded conformation. Notably, the FrMLV RBD (frRBD) primarily engages the third extracellular loop (ECL3) of CAT1-a region marked by substantial species-specific variation that likely governs cross-species viral tropism. Together, our structural and biochemical results elucidate the molecular mechanism of substrate recognition and transport by mCAT1, and unveil the molecular basis for FrMLV receptor specificity. These findings provide a valuable framework for structure-based drug design targeting CAT1 in cancer and infectious diseases.
History
DepositionApr 1, 2025-
Header (metadata) releaseFeb 11, 2026-
Map releaseFeb 11, 2026-
UpdateFeb 11, 2026-
Current statusFeb 11, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_63995.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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AxesZ (Sec.)Y (Row.)X (Col.)
1.09 Å/pix.
x 256 pix.
= 278.272 Å
1.09 Å/pix.
x 256 pix.
= 278.272 Å
1.09 Å/pix.
x 256 pix.
= 278.272 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.087 Å
Density
Contour LevelBy AUTHOR: 0.2
Minimum - Maximum-0.0016669249 - 3.516625
Average (Standard dev.)0.00143802 (±0.025977734)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 278.272 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_63995_half_map_1.map
Projections & Slices
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Half map: #1

Fileemd_63995_half_map_2.map
Projections & Slices
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Sample components

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Entire : The structure of mCAT1 in complex with its substrate ornithine an...

EntireName: The structure of mCAT1 in complex with its substrate ornithine and the RBD of FrMLV
Components
  • Complex: The structure of mCAT1 in complex with its substrate ornithine and the RBD of FrMLV
    • Protein or peptide: High affinity cationic amino acid transporter 1
    • Protein or peptide: Surface protein
  • Ligand: L-ornithine
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: The structure of mCAT1 in complex with its substrate ornithine an...

SupramoleculeName: The structure of mCAT1 in complex with its substrate ornithine and the RBD of FrMLV
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Mus musculus (house mouse)

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Macromolecule #1: High affinity cationic amino acid transporter 1

MacromoleculeName: High affinity cationic amino acid transporter 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 64.978207 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MGCKNLLGLG QQMLRRKVVD CSREESRLSR CLNTYDLVAL GVGSTLGAGV YVLAGAVARE NAGPAIVISF LIAALASVLA GLCYGEFGA RVPKTGSAYL YSYVTVGELW AFITGWNLIL SYIIGTSSVA RAWSATFDEL IGKPIGEFSR QHMALNAPGV L AQTPDIFA ...String:
MGCKNLLGLG QQMLRRKVVD CSREESRLSR CLNTYDLVAL GVGSTLGAGV YVLAGAVARE NAGPAIVISF LIAALASVLA GLCYGEFGA RVPKTGSAYL YSYVTVGELW AFITGWNLIL SYIIGTSSVA RAWSATFDEL IGKPIGEFSR QHMALNAPGV L AQTPDIFA VIIIIILTGL LTLGVKESAM VNKIFTCINV LVLCFIVVSG FVKGSIKNWQ LTEKNFSCNN NDTNVKYGEG GF MPFGFSG VLSGAATCFY AFVGFDCIAT TGEEVKNPQK AIPVGIVASL LICFIAYFGV SAALTLMMPY FCLDIDSPLP GAF KHQGWE EAKYAVAIGS LCALSTSLLG SMFPMPRVIY AMAEDGLLFK FLAKINNRTK TPVIATVTSG AIAAVMAFLF ELKD LVDLM SIGTLLAYSL VAACVLVLRY QPEQPNLVYQ MARTTEELDR VDQNELVSAS ESQTGFLPVA EKFSLKSILS PKNVE PSKF SGLIVNISAG LLAALIITVC IVAVLGREAL AEGTLWAVFV MTGSVLLCML VTGIIWRQPE SKTKLSFKVP FVPVLP VLS IFVNIYLMMQ LDQGTWVRFA VWMLIGFTIY FGYGIWHS

UniProtKB: High affinity cationic amino acid transporter 1

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Macromolecule #2: Surface protein

MacromoleculeName: Surface protein / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Friend murine leukemia virus (ISOLATE 57)
Molecular weightTheoretical: 25.411256 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: APGSSPHQVY NITWEVTNGD RETVWAISGN HPLWTWWPVL TPDLCMLALS GPPHWGLEYQ APYSSPPGPP CCSGSSGSSA GCSRDCDEP LTSLTPRCNT AWNRLKLDQV THKSSEGFYV CPGSHRPREA KSCGGPDSFY CASWGCETTG RVYWKPSSSW D YITVDNNL ...String:
APGSSPHQVY NITWEVTNGD RETVWAISGN HPLWTWWPVL TPDLCMLALS GPPHWGLEYQ APYSSPPGPP CCSGSSGSSA GCSRDCDEP LTSLTPRCNT AWNRLKLDQV THKSSEGFYV CPGSHRPREA KSCGGPDSFY CASWGCETTG RVYWKPSSSW D YITVDNNL TTSQAVQVCK DNKWCNPLAI QFTNAGKQVT SWTTGHYWGL RLYVSGRDPG LTFGIRLRYQ N

UniProtKB: Envelope glycoprotein

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Macromolecule #5: L-ornithine

MacromoleculeName: L-ornithine / type: ligand / ID: 5 / Number of copies: 1 / Formula: ORN
Molecular weightTheoretical: 132.161 Da
Chemical component information

ChemComp-ORN:
L-ornithine

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Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 1 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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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: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 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: 3.65 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 9.03) / Number images used: 106963
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: MAXIMUM LIKELIHOOD

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