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Yorodumi- EMDB-18379: Structure of human Asc1/CD98hc heteromeric amino acid transporter -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-18379 | |||||||||
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Title | Structure of human Asc1/CD98hc heteromeric amino acid transporter | |||||||||
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Keywords | Heteromeric amino acid transporter Transporter APC transporter / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information D-alanine transmembrane transport / D-serine transmembrane transport / positive regulation of synaptic transmission, glycinergic / L-serine transmembrane transporter activity / glycine transport / neutral L-amino acid secondary active transmembrane transporter activity / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / methionine transport / tyrosine transport / L-histidine transport ...D-alanine transmembrane transport / D-serine transmembrane transport / positive regulation of synaptic transmission, glycinergic / L-serine transmembrane transporter activity / glycine transport / neutral L-amino acid secondary active transmembrane transporter activity / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / methionine transport / tyrosine transport / L-histidine transport / apical pole of neuron / aromatic amino acid transmembrane transporter activity / negative regulation of brown fat cell differentiation / amino acid transport complex / L-amino acid transmembrane transporter activity / : / L-leucine import across plasma membrane / L-alanine transmembrane transporter activity / isoleucine transport / L-alanine import across plasma membrane / phenylalanine transport / valine transport / L-leucine transmembrane transporter activity / amino acid transmembrane transport / calcium:sodium antiporter activity / L-leucine transport / thyroid hormone transport / proline transport / neutral amino acid transport / Amino acid transport across the plasma membrane / neutral L-amino acid transmembrane transporter activity / Tryptophan catabolism / exogenous protein binding / anchoring junction / Basigin interactions / amino acid transport / response to exogenous dsRNA / tryptophan transport / basal plasma membrane / calcium ion transport / double-stranded RNA binding / melanosome / virus receptor activity / basolateral plasma membrane / carbohydrate metabolic process / cadherin binding / symbiont entry into host cell / apical plasma membrane / protein heterodimerization activity / lysosomal membrane / synapse / cell surface / protein homodimerization activity / RNA binding / extracellular exosome / nucleoplasm / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.0 Å | |||||||||
Authors | Martinez-Molledo M / Rullo-Tubau J / Errasti-Murugarren E / Palacin M / Llorca O | |||||||||
Funding support | Spain, 1 items
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Citation | Journal: Nat Commun / Year: 2024 Title: Structure and mechanisms of transport of human Asc1/CD98hc amino acid transporter. Authors: Josep Rullo-Tubau / Maria Martinez-Molledo / Paola Bartoccioni / Ignasi Puch-Giner / Ángela Arias / Suwipa Saen-Oon / Camille Stephan-Otto Attolini / Rafael Artuch / Lucía Díaz / Víctor ...Authors: Josep Rullo-Tubau / Maria Martinez-Molledo / Paola Bartoccioni / Ignasi Puch-Giner / Ángela Arias / Suwipa Saen-Oon / Camille Stephan-Otto Attolini / Rafael Artuch / Lucía Díaz / Víctor Guallar / Ekaitz Errasti-Murugarren / Manuel Palacín / Oscar Llorca / Abstract: Recent cryoEM studies elucidated details of the structural basis for the substrate selectivity and translocation of heteromeric amino acid transporters. However, Asc1/CD98hc is the only neutral ...Recent cryoEM studies elucidated details of the structural basis for the substrate selectivity and translocation of heteromeric amino acid transporters. However, Asc1/CD98hc is the only neutral heteromeric amino acid transporter that can function through facilitated diffusion, and the only one that efficiently transports glycine and D-serine, and thus has a regulatory role in the central nervous system. Here we use cryoEM, ligand-binding simulations, mutagenesis, transport assays, and molecular dynamics to define human Asc1/CD98hc determinants for substrate specificity and gain insights into the mechanisms that govern substrate translocation by exchange and facilitated diffusion. The cryoEM structure of Asc1/CD98hc is determined at 3.4-3.8 Å resolution, revealing an inward-facing semi-occluded conformation. We find that Ser 246 and Tyr 333 are essential for Asc1/CD98hc substrate selectivity and for the exchange and facilitated diffusion modes of transport. Taken together, these results reveal the structural bases for ligand binding and transport features specific to human Asc1. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_18379.map.gz | 22.1 MB | EMDB map data format | |
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Header (meta data) | emd-18379-v30.xml emd-18379.xml | 20 KB 20 KB | Display Display | EMDB header |
Images | emd_18379.png | 21.7 KB | ||
Filedesc metadata | emd-18379.cif.gz | 6.8 KB | ||
Others | emd_18379_additional_1.map.gz emd_18379_half_map_1.map.gz emd_18379_half_map_2.map.gz | 97.1 MB 95.7 MB 95.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-18379 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-18379 | HTTPS FTP |
-Validation report
Summary document | emd_18379_validation.pdf.gz | 760.7 KB | Display | EMDB validaton report |
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Full document | emd_18379_full_validation.pdf.gz | 760.3 KB | Display | |
Data in XML | emd_18379_validation.xml.gz | 13.1 KB | Display | |
Data in CIF | emd_18379_validation.cif.gz | 15.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-18379 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-18379 | HTTPS FTP |
-Related structure data
Related structure data | 8qeyMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_18379.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.831 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: #1
File | emd_18379_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_18379_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_18379_half_map_2.map | ||||||||||||
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Density Histograms |
-Sample components
-Entire : Asc1/CD98hc
Entire | Name: Asc1/CD98hc |
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Components |
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-Supramolecule #1: Asc1/CD98hc
Supramolecule | Name: Asc1/CD98hc / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Asc-type amino acid transporter 1
Macromolecule | Name: Asc-type amino acid transporter 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 56.837504 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MAGHTQQPSG RGNPRPAPSP SPVPGTVPGA SERVALKKEI GLLSACTIII GNIIGSGIFI SPKGVLEHSG SVGLALFVWV LGGGVTALG SLCYAELGVA IPKSGGDYAY VTEIFGGLAG FLLLWSAVLI MYPTSLAVIS MTFSNYVLQP VFPNCIPPTT A SRVLSMAC ...String: MAGHTQQPSG RGNPRPAPSP SPVPGTVPGA SERVALKKEI GLLSACTIII GNIIGSGIFI SPKGVLEHSG SVGLALFVWV LGGGVTALG SLCYAELGVA IPKSGGDYAY VTEIFGGLAG FLLLWSAVLI MYPTSLAVIS MTFSNYVLQP VFPNCIPPTT A SRVLSMAC LMLLTWVNSS SVRWATRIQD MFTGGKLLAL SLIIGVGLLQ IFQGHFEELR PSNAFAFWMT PSVGHLALAF LQ GSFAFSG WNFLNYVTEE MVDARKNLPR AIFISIPLVT FVYTFTNIAY FTAMSPQELL SSNAVAVTFG EKLLGYFSWV MPV SVALST FGGINGYLFT YSRLCFSGAR EGHLPSLLAM IHVRHCTPIP ALLVCCGATA VIMLVGDTYT LINYVSFINY LCYG VTILG LLLLRWRRPA LHRPIKVNLL IPVAYLVFWA FLLVFSFISE PMVCGVGVII ILTGVPIFFL GVFWRSKPKC VHRLT ESMT HWGQELCFVV YPQDAPEEEE NGPCPPSLLP ATDKPSKPQ UniProtKB: Asc-type amino acid transporter 1 |
-Macromolecule #2: 4F2 cell-surface antigen heavy chain
Macromolecule | Name: 4F2 cell-surface antigen heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 68.056688 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MELQPPEASI AVVSIPRQLP GSHSEAGVQG LSAGDDSELG SHCVAQTGLE LLASGDPLPS ASQNAEMIET GSDCVTQAGL QLLASSDPP ALASKNAEVT GTMSQDTEVD MKEVELNELE PEKQPMNAAS GAAMSLAGAE KNGLVKIKVA EDEAEAAAAA K FTGLSKEE ...String: MELQPPEASI AVVSIPRQLP GSHSEAGVQG LSAGDDSELG SHCVAQTGLE LLASGDPLPS ASQNAEMIET GSDCVTQAGL QLLASSDPP ALASKNAEVT GTMSQDTEVD MKEVELNELE PEKQPMNAAS GAAMSLAGAE KNGLVKIKVA EDEAEAAAAA K FTGLSKEE LLKVAGSPGW VRTRWALLLL FWLGWLGMLA GAVVIIVRAP RCRELPAQKW WHTGALYRIG DLQAFQGHGA GN LAGLKGR LDYLSSLKVK GLVLGPIHKN QKDDVAQTDL LQIDPNFGSK EDFDSLLQSA KKKSIRVILD LTPNYRGENS WFS TQVDTV ATKVKDALEF WLQAGVDGFQ VRDIENLKDA SSFLAEWQNI TKGFSEDRLL IAGTNSSDLQ QILSLLESNK DLLL TSSYL SDSGSTGEHT KSLVTQYLNA TGNRWCSWSL SQARLLTSFL PAQLLRLYQL MLFTLPGTPV FSYGDEIGLD AAALP GQPM EAPVMLWDES SFPDIPGAVS ANMTVKGQSE DPGSLLSLFR RLSDQRSKER SLLHGDFHAF SAGPGLFSYI RHWDQN ERF LVVLNFGDVG LSAGLQASDL PASASLPAKA DLLLSTQPGR EEGSPLELER LKLEPHEGLL LRFPYAA UniProtKB: Amino acid transporter heavy chain SLC3A2 |
-Macromolecule #5: Digitonin
Macromolecule | Name: Digitonin / type: ligand / ID: 5 / Number of copies: 1 / Formula: AJP |
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Molecular weight | Theoretical: 1.229312 KDa |
Chemical component information | ChemComp-AJP: |
-Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 1 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1.2 mg/mL | ||||||||||||
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Buffer | pH: 8 Component:
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Grid | Model: Quantifoil R0.6/1 / Material: COPPER / Pretreatment - Type: GLOW DISCHARGE | ||||||||||||
Vitrification | Cryogen name: ETHANE-PROPANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 31696 / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER / Details: AlphaFold |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 139507 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |