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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-9722 | |||||||||||||||||||||
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Title | human LAT1-4F2hc complex bound with BCH | |||||||||||||||||||||
![]() | cryo EM map | |||||||||||||||||||||
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Function / homology | ![]() L-tryptophan transmembrane transporter activity / alanine transport / L-tryptophan transmembrane transport / positive regulation of L-leucine import across plasma membrane / cellular response to L-arginine / thyroid hormone transmembrane transporter activity / neutral L-amino acid secondary active transmembrane transporter activity / amino acid import across plasma membrane / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / methionine transport ...L-tryptophan transmembrane transporter activity / alanine transport / L-tryptophan transmembrane transport / positive regulation of L-leucine import across plasma membrane / cellular response to L-arginine / thyroid hormone transmembrane transporter activity / neutral L-amino acid secondary active transmembrane transporter activity / amino acid import across plasma membrane / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / methionine transport / tyrosine transport / L-histidine transport / apical pole of neuron / aromatic amino acid transmembrane transporter activity / amino acid transport complex / L-leucine import across plasma membrane / L-alanine transmembrane transporter activity / isoleucine transport / L-alanine import across plasma membrane / L-amino acid transmembrane transporter activity / phenylalanine transport / valine transport / amino acid transmembrane transport / L-leucine transmembrane transporter activity / calcium:sodium antiporter activity / L-leucine transport / thyroid hormone transport / proline transport / positive regulation of cytokine production involved in immune response / negative regulation of vascular associated smooth muscle cell apoptotic process / neutral amino acid transport / amino acid transmembrane transporter activity / external side of apical plasma membrane / Amino acid transport across the plasma membrane / neutral L-amino acid transmembrane transporter activity / Tryptophan catabolism / exogenous protein binding / xenobiotic transport / anchoring junction / response to muscle activity / antiporter activity / Basigin interactions / microvillus membrane / amino acid transport / positive regulation of interleukin-4 production / response to exogenous dsRNA / positive regulation of interleukin-17 production / tryptophan transport / transport across blood-brain barrier / response to hyperoxia / cellular response to glucose starvation / positive regulation of glial cell proliferation / negative regulation of autophagy / basal plasma membrane / liver regeneration / positive regulation of type II interferon production / peptide antigen binding / calcium ion transport / double-stranded RNA binding / melanosome / virus receptor activity / cellular response to lipopolysaccharide / basolateral plasma membrane / carbohydrate metabolic process / cadherin binding / symbiont entry into host cell / protein heterodimerization activity / apical plasma membrane / lysosomal membrane / negative regulation of gene expression / intracellular membrane-bounded organelle / synapse / cell surface / protein homodimerization activity / RNA binding / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytosol Similarity search - Function | |||||||||||||||||||||
Biological species | ![]() | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||||||||||||||
![]() | Yan RH / Zhao X / Lei JL / Zhou Q | |||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex. Authors: Renhong Yan / Xin Zhao / Jianlin Lei / Qiang Zhou / ![]() Abstract: The L-type amino acid transporter 1 (LAT1; also known as SLC7A5) catalyses the cross-membrane flux of large neutral amino acids in a sodium- and pH-independent manner. LAT1, an antiporter of the ...The L-type amino acid transporter 1 (LAT1; also known as SLC7A5) catalyses the cross-membrane flux of large neutral amino acids in a sodium- and pH-independent manner. LAT1, an antiporter of the amino acid-polyamine-organocation superfamily, also catalyses the permeation of thyroid hormones, pharmaceutical drugs, and hormone precursors such as L-3,4-dihydroxyphenylalanine across membranes. Overexpression of LAT1 has been observed in a wide range of tumour cells, and it is thus a potential target for anti-cancer drugs. LAT1 forms a heteromeric amino acid transporter complex with 4F2 cell-surface antigen heavy chain (4F2hc; also known as SLC3A2)-a type II membrane glycoprotein that is essential for the stability of LAT1 and for its localization to the plasma membrane. Despite extensive cell-based characterization of the LAT1-4F2hc complex and structural determination of its homologues in bacteria, the interactions between LAT1 and 4F2hc and the working mechanism of the complex remain largely unknown. Here we report the cryo-electron microscopy structures of human LAT1-4F2hc alone and in complex with the inhibitor 2-amino-2-norbornanecarboxylic acid at resolutions of 3.3 Å and 3.5 Å, respectively. LAT1 exhibits an inward open conformation. Besides a disulfide bond association, LAT1 also interacts extensively with 4F2hc on the extracellular side, within the membrane, and on the intracellular side. Biochemical analysis reveals that 4F2hc is essential for the transport activity of the complex. Together, our characterizations shed light on the architecture of the LAT1-4F2hc complex, and provide insights into its function and the mechanisms through which it might be associated with disease. | |||||||||||||||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.1 KB 14.1 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.1 KB | Display | ![]() |
Images | ![]() | 52.1 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6irtMC ![]() 0678C ![]() 0679C ![]() 9721C ![]() 6irsC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | cryo EM map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.091 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : human LAT1-4F2hc complex bound with BCH
Entire | Name: human LAT1-4F2hc complex bound with BCH |
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Components |
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-Supramolecule #1: human LAT1-4F2hc complex bound with BCH
Supramolecule | Name: human LAT1-4F2hc complex bound with BCH / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Molecular weight | Theoretical: 100 KDa |
-Macromolecule #1: 4F2 cell-surface antigen heavy chain
Macromolecule | Name: 4F2 cell-surface antigen heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 70.160828 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MAHHHHHHHH HHSGRELQPP EASIAVVSIP RQLPGSHSEA GVQGLSAGDD SETGSDCVTQ AGLQLLASSD PPALASKNAE VTVETGFHH VSQADIEFLT SIDPTASASG SAGITGTMSQ DTEVDMKEVE LNELEPEKQP MNAASGAAMS LAGAEKNGLV K IKVAEDEA ...String: MAHHHHHHHH HHSGRELQPP EASIAVVSIP RQLPGSHSEA GVQGLSAGDD SETGSDCVTQ AGLQLLASSD PPALASKNAE VTVETGFHH VSQADIEFLT SIDPTASASG SAGITGTMSQ DTEVDMKEVE LNELEPEKQP MNAASGAAMS LAGAEKNGLV K IKVAEDEA EAAAAAKFTG LSKEELLKVA GSPGWVRTRW ALLLLFWLGW LGMLAGAVVI IVRAPRCREL PAQKWWHTGA LY RIGDLQA FQGHGAGNLA GLKGRLDYLS SLKVKGLVLG PIHKNQKDDV AQTDLLQIDP NFGSKEDFDS LLQSAKKKSI RVI LDLTPN YRGENSWFST QVDTVATKVK DALEFWLQAG VDGFQVRDIE NLKDASSFLA EWQNITKGFS EDRLLIAGTN SSDL QQILS LLESNKDLLL TSSYLSDSGS TGEHTKSLVT QYLNATGNRW CSWSLSQARL LTSFLPAQLL RLYQLMLFTL PGTPV FSYG DEIGLDAAAL PGQPMEAPVM LWDESSFPDI PGAVSANMTV KGQSEDPGSL LSLFRRLSDQ RSKERSLLHG DFHAFS AGP GLFSYIRHWD QNERFLVVLN FGDVGLSAGL QASDLPASAS LPAKADLLLS TQPGREEGSP LELERLKLEP HEGLLLR FP YAALE |
-Macromolecule #2: Large neutral amino acids transporter small subunit 1
Macromolecule | Name: Large neutral amino acids transporter small subunit 1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 57.244934 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MADYKDDDDK SGPDEVDASG RAGAGPKRRA LAAPAAEEKE EAREKMLAAK SADGSEPAGE GEGVTLQRNI TLLNGVAIIV GTIIGSGIF VTPTGVLKEA GSPGLALVVW AACGVFSIVG ALCYAELGTT ISKSGGDYAY MLEVYGSLPA FLKLWIELLI I RPSSQYIV ...String: MADYKDDDDK SGPDEVDASG RAGAGPKRRA LAAPAAEEKE EAREKMLAAK SADGSEPAGE GEGVTLQRNI TLLNGVAIIV GTIIGSGIF VTPTGVLKEA GSPGLALVVW AACGVFSIVG ALCYAELGTT ISKSGGDYAY MLEVYGSLPA FLKLWIELLI I RPSSQYIV ALVFATYLLK PLFPTCPVPE EAAKLVACLC VLLLTAVNCY SVKAATRVQD AFAAAKLLAL ALIILLGFVQ IG KGDVSNL DPNFSFEGTK LDVGNIVLAL YSGLFAYGGW NYLNFVTEEM INPYRNLPLA IIISLPIVTL VYVLTNLAYF TTL STEQML SSEAVAVDFG NYHLGVMSWI IPVFVGLSCF GSVNGSLFTS SRLFFVGSRE GHLPSILSMI HPQLLTPVPS LVFT CVMTL LYAFSKDIFS VINFFSFFNW LCVALAIIGM IWLRHRKPEL ERPIKVNLAL PVFFILACLF LIAVSFWKTP VECGI GFTI ILSGLPVYFF GVWWKNKPKW LLQGIFSTTV LCQKLMQVVP QET |
-Macromolecule #4: 1,2-DIACYL-GLYCEROL-3-SN-PHOSPHATE
Macromolecule | Name: 1,2-DIACYL-GLYCEROL-3-SN-PHOSPHATE / type: ligand / ID: 4 / Number of copies: 2 / Formula: 3PH |
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Molecular weight | Theoretical: 704.998 Da |
Chemical component information | ![]() ChemComp-3PH: |
-Macromolecule #5: (1S,2S,4R)-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid
Macromolecule | Name: (1S,2S,4R)-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid type: ligand / ID: 5 / Number of copies: 1 / Formula: AUU |
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Molecular weight | Theoretical: 155.194 Da |
Chemical component information | ![]() ChemComp-AUU: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 48.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |