+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-0679 | |||||||||||||||||||||
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Title | human LAT1-4F2hc complex bound with BCH, focused refined on BCH | |||||||||||||||||||||
Map data | ||||||||||||||||||||||
Sample |
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Function / homology | Function and homology information 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 / amino acid import across plasma membrane / methionine transport / tyrosine transport / L-histidine 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 / amino acid import across plasma membrane / methionine transport / tyrosine transport / L-histidine transport / aromatic amino acid transmembrane transporter activity / amino acid transport complex / L-leucine import across plasma membrane / isoleucine transport / L-amino acid transmembrane transporter activity / phenylalanine transport / valine transport / amino acid transmembrane transport / L-leucine transmembrane transporter 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 / xenobiotic transport / response to muscle activity / antiporter activity / Basigin interactions / microvillus membrane / positive regulation of interleukin-4 production / positive regulation of interleukin-17 production / positive regulation of glial cell proliferation / tryptophan transport / transport across blood-brain barrier / response to hyperoxia / cellular response to glucose starvation / basal plasma membrane / liver regeneration / negative regulation of autophagy / positive regulation of type II interferon production / peptide antigen binding / basolateral plasma membrane / cellular response to lipopolysaccharide / apical plasma membrane / lysosomal membrane / negative regulation of gene expression / intracellular membrane-bounded organelle / extracellular exosome / membrane / plasma membrane / cytosol Similarity search - Function | |||||||||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.7 Å | |||||||||||||||||||||
Authors | Yan RH / Zhao X / Lei JL / Zhou Q | |||||||||||||||||||||
Funding support | China, 6 items
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Citation | Journal: Nature / Year: 2019 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
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_0679.map.gz | 59 MB | EMDB map data format | |
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Header (meta data) | emd-0679-v30.xml emd-0679.xml | 12.3 KB 12.3 KB | Display Display | EMDB header |
Images | emd_0679.png | 62.9 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-0679 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0679 | HTTPS FTP |
-Validation report
Summary document | emd_0679_validation.pdf.gz | 79.2 KB | Display | EMDB validaton report |
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Full document | emd_0679_full_validation.pdf.gz | 78.3 KB | Display | |
Data in XML | emd_0679_validation.xml.gz | 493 B | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0679 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0679 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_0679.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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
-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: all |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 100 KDa |
-Macromolecule #1: LAT1
Macromolecule | Name: LAT1 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MADYKDDDDK SGPDEVDASG RAGAGPKRRA LAAPAAEEKE EAREKMLAAK SADGSEPAGE GEGVTLQRNI TLLNGVAIIV GTIIGSGIF VTPTGVLKEA GSPGLALVVW AACGVFSIVG ALCYAELGTT ISKSGGDYAY M LEVYGSLP AFLKLWIELL IIRPSSQYIV ...String: MADYKDDDDK SGPDEVDASG RAGAGPKRRA LAAPAAEEKE EAREKMLAAK SADGSEPAGE GEGVTLQRNI TLLNGVAIIV GTIIGSGIF VTPTGVLKEA GSPGLALVVW AACGVFSIVG ALCYAELGTT ISKSGGDYAY M LEVYGSLP AFLKLWIELL IIRPSSQYIV ALVFATYLLK PLFPTCPVPE EAAKLVACLC VL LLTAVNC YSVKAATRVQ DAFAAAKLLA LALIILLGFV QIGKGDVSNL DPNFSFEGTK LDV GNIVLA LYSGLFAYGG WNYLNFVTEE MINPYRNLPL AIIISLPIVT LVYVLTNLAY FTTL STEQM LSSEAVAVDF GNYHLGVMSW IIPVFVGLSC FGSVNGSLFT SSRLFFVGSR EGHLP SILS MIHPQLLTPV PSLVFTCVMT LLYAFSKDIF SVINFFSFFN WLCVALAIIG MIWLRH RKP ELERPIKVNL ALPVFFILAC LFLIAVSFWK TPVECGIGFT IILSGLPVYF FGVWWKN KP KWLLQGIFST TVLCQKLMQV VPQET |
-Macromolecule #2: 4F2hc
Macromolecule | Name: 4F2hc / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MAHHHHHHHH HHSGRELQPP EASIAVVSIP RQLPGSHSEA GVQGLSAGDD SETGSDCVTQ AGLQLLASSD PPALASKNAE VTVETGFHHV SQADI EFLT SIDPTASASG SAGITGTMSQ DTEVDMKEVE LNELEPEKQP MNAASGAAMS LAGAEKNGLV KIKVAEDEAE ...String: MAHHHHHHHH HHSGRELQPP EASIAVVSIP RQLPGSHSEA GVQGLSAGDD SETGSDCVTQ AGLQLLASSD PPALASKNAE VTVETGFHHV SQADI EFLT SIDPTASASG SAGITGTMSQ DTEVDMKEVE LNELEPEKQP MNAASGAAMS LAGAEKNGLV KIKVAEDEAE AAAAAK FTG LSKEELLKVA GSPGWVRTRW ALLLLFWLGW LGMLAGAVVI IVRAPRCREL PAQKWWHTGA LYRIGDLQAF QGHGAGN LA GLKGRLDYLS SLKVKGLVLG PIHKNQKDDV AQTDLLQIDP NFGSKEDFDS LLQSAKKKSI RVILDLTPNY RGENSWFS T QVDTVATKVK DALEFWLQAG VDGFQVRDIE NLKDASSFLA EWQNITKGFS EDRLLIAGTN SSDLQQILSL LESNKDLLL TSSYLSDSGS TGEHTKSLVT QYLNATGNRW CSWSLSQARL LTSFLPAQLL RLYQLMLFTL PGTPVFSYGD EIGLDAAALP GQPMEAPVM LWDESSFPDI PGAVSANMTV KGQSEDPGSL LSLFRRLSDQ RSKERSLLHG DFHAFSAGPG LFSYIRHWDQ N ERFLVVLN FGDVGLSAGL QASDLPASAS LPAKADLLLS TQPGREEGSP LELERLKLEP HEGLLLRFPY AALE |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |