[English] 日本語
Yorodumi
- EMDB-61326: Structure of LAT4 in complex with digitonin -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-61326
TitleStructure of LAT4 in complex with digitonin
Map datasharpened map of LAT4 in complex with digitonin
Sample
  • Complex: Large neutral amino acids transporter small subunit 4
    • Protein or peptide: Large neutral amino acids transporter small subunit 4
  • Ligand: Digitonin
KeywordsLAT4 / SLC43A2 / amino acid transporter / MEMBRANE PROTEIN
Function / homology
Function and homology information


negative regulation of amino acid transport / negative regulation of L-leucine import across plasma membrane / L-phenylalanine transmembrane transporter activity / L-methionine transmembrane transporter activity / L-isoleucine transmembrane transporter activity / phenylalanine transport / methionine transport / L-leucine transmembrane transporter activity / isoleucine transport / L-amino acid transmembrane transporter activity ...negative regulation of amino acid transport / negative regulation of L-leucine import across plasma membrane / L-phenylalanine transmembrane transporter activity / L-methionine transmembrane transporter activity / L-isoleucine transmembrane transporter activity / phenylalanine transport / methionine transport / L-leucine transmembrane transporter activity / isoleucine transport / L-amino acid transmembrane transporter activity / L-leucine transport / neutral amino acid transport / neutral L-amino acid transmembrane transporter activity / Amino acid transport across the plasma membrane / amino acid transmembrane transporter activity / amino acid transport / basolateral plasma membrane / plasma membrane
Similarity search - Function
Major facilitator superfamily / Major Facilitator Superfamily / MFS transporter superfamily
Similarity search - Domain/homology
Large neutral amino acids transporter small subunit 4
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.8 Å
AuthorsYin YX / Ding D / Lu YS / Chen HY
Funding support China, 3 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)82030081 China
National Natural Science Foundation of China (NSFC)81874235 China
National Natural Science Foundation of China (NSFC)82173386 China
CitationJournal: EMBO J / Year: 2026
Title: Structures of the neutral amino acid transporter LAT4 provide insights into antitumor effects of its inhibitor tubeimoside-1.
Authors: Dian Ding / Yishuo Lu / Jingyi Yang / Hongyi Chen / Peijun Jiang / Yan Jin / Jianyuan Luo / Guangxi Wang / Yuxin Yin /
Abstract: Methionine restriction has emerged as a promising strategy for extending lifespan and enhancing cancer therapy. LAT4, an amino acid transporter encoded by SLC43A2, is frequently overexpressed in ...Methionine restriction has emerged as a promising strategy for extending lifespan and enhancing cancer therapy. LAT4, an amino acid transporter encoded by SLC43A2, is frequently overexpressed in multiple cancers and critically contributes to systemic methionine accumulation. However, the structural basis of LAT4 function remains poorly understood, and no effective inhibitors have been developed to date. In this study, we present high-resolution cryo-electron microscopy structures of LAT4 and the related SLC43A3-encoded purine transporter ENBT1. The phenylalanine-bound structure of LAT4 enables the characterization of the substrate binding pocket. Comparison of the outward-facing ENBT1 and inward-facing LAT4 structures identifies key residues involved in the methionine transport process. Structural analysis of digitonin binding to the central cavity of LAT4 enabled identification of tubeimoside-1 (TBM-1) as a potent inhibitor of LAT4-mediated methionine uptake. We demonstrate that tubeimoside-1 reduces methionine uptake in B16F10 cancer cells. Furthermore, TBM-1 suppresses tumor progression in the MMTV-PyVT mouse model of breast cancer through systemic methionine restriction. Our study provides insights into the LAT4 transport mechanism and identifies tubeimoside-1 as a potent inhibitor of methionine uptake and establishes a foundation for developing LAT4-targeting therapeutics to restrict methionine uptake.
History
DepositionAug 27, 2024-
Header (metadata) releaseMar 11, 2026-
Map releaseMar 11, 2026-
UpdateSep 9, 2026-
Current statusSep 9, 2026Processing site: PDBc / Status: Released

-
Structure visualization

Supplemental images

emd_61326.png

Downloads & links

-
Map

FileDownload / File: emd_61326.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationsharpened map of LAT4 in complex with digitonin
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 300 pix.
= 250.2 Å		0.83 Å/pix.
x 300 pix.
= 250.2 Å		0.83 Å/pix.
x 300 pix.
= 250.2 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.834 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.155
Minimum - Maximum-0.6928811 - 1.0274794
Average (Standard dev.)-0.0005570327 (±0.01773567)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 250.2 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: half-b map of LAT4 in complex with digitonin

Fileemd_61326_half_map_1.map
Annotationhalf-b map of LAT4 in complex with digitonin
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: half-a map of LAT4 in complex with digitonin

Fileemd_61326_half_map_2.map
Annotationhalf-a map of LAT4 in complex with digitonin
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Large neutral amino acids transporter small subunit 4

EntireName: Large neutral amino acids transporter small subunit 4
Components
  • Complex: Large neutral amino acids transporter small subunit 4
    • Protein or peptide: Large neutral amino acids transporter small subunit 4
  • Ligand: Digitonin

-
Supramolecule #1: Large neutral amino acids transporter small subunit 4

SupramoleculeName: Large neutral amino acids transporter small subunit 4 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Large neutral amino acids transporter small subunit 4

MacromoleculeName: Large neutral amino acids transporter small subunit 4 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 62.797562 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MAPTLATAHR RRWWMACTAV LENLLFSAVL LGWGSLLIML KSEGFYSYLC TEPENVTNGT VGGTAEPGHE EVSWMNGWLS CQAQDEMLN LAFTVGSFLL SAITLPLGIV MDKYGPRKLR LLGSACFAVS CLLIAYGASK PNALSVLIFI ALALNGFGGM C MTFTSLTL ...String:
MAPTLATAHR RRWWMACTAV LENLLFSAVL LGWGSLLIML KSEGFYSYLC TEPENVTNGT VGGTAEPGHE EVSWMNGWLS CQAQDEMLN LAFTVGSFLL SAITLPLGIV MDKYGPRKLR LLGSACFAVS CLLIAYGASK PNALSVLIFI ALALNGFGGM C MTFTSLTL PNMFGDLRST FIALMIGSYA SSAVTFPGIK LIYDAGVSFI VVLVVWAGCS GLVFLNCFFN WPLEPFPGPE DM DYSVKIK FSWLGFDHKI TGKQFYKQVT TVGRRLSVGS SMRSAKEQVA LQEGHKLCLS TVDLEVKCQP DAAVAPSFMH SVF SPILLL SLVTMCVTQL RLIFYMGAMN NILKFLVSGD QKTVGLYTSI FGVLQLLCLL TAPVIGYIMD WRLKECEDAS EEPE EKDAN QGEKKKKKRD RQIQKITNAM RAFAFTNLLL VGFGVTCLIP NLPLQILSFI LHTIVRGFIH SAVGGLYAAV YPSTQ FGSL TGLQSLISAL FALLQQPLFL AMMGPLQGDP LWVNVGLLLL SLLGFCLPLY LICYRRQLER QLQQRQEDDK LFLKIN GSS NQEAFV

UniProtKB: Large neutral amino acids transporter small subunit 4

-
Macromolecule #2: Digitonin

MacromoleculeName: Digitonin / type: ligand / ID: 2 / Number of copies: 1 / Formula: AJP
Molecular weightTheoretical: 1.229312 KDa
Chemical component information

ChemComp-AJP:
Digitonin / detergent*YM

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 56.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.5 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 177241
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more