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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-9850 | ||||||||||||
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Title | CD98hc extracellular domain bound to HBJ127 Fab and MEM-108 Fab | ||||||||||||
![]() | Masked, sharpend map calculated with the mask covering CD98hc-ED and two Fabs. | ||||||||||||
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Function / homology | ![]() 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 / amino acid transport complex / L-leucine import across plasma membrane / L-alanine transmembrane transporter activity ...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 / amino acid transport complex / 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 / calcium:sodium antiporter activity / L-leucine transport / thyroid hormone transport / proline 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 / virus receptor activity / melanosome / basolateral plasma membrane / carbohydrate metabolic process / cadherin binding / apical plasma membrane / symbiont entry into host cell / protein heterodimerization activity / lysosomal membrane / synapse / cell surface / protein homodimerization activity / RNA binding / extracellular exosome / nucleoplasm / membrane / plasma membrane Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.1 Å | ||||||||||||
![]() | Lee Y / Nishizawa T / Kusakizako T / Oda K / Ishitani R / Yokoyama T / Nakane T / Shirouzu M / Nureki O | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM structure of the human L-type amino acid transporter 1 in complex with glycoprotein CD98hc. Authors: Yongchan Lee / Pattama Wiriyasermkul / Chunhuan Jin / Lili Quan / Ryuichi Ohgaki / Suguru Okuda / Tsukasa Kusakizako / Tomohiro Nishizawa / Kazumasa Oda / Ryuichiro Ishitani / Takeshi ...Authors: Yongchan Lee / Pattama Wiriyasermkul / Chunhuan Jin / Lili Quan / Ryuichi Ohgaki / Suguru Okuda / Tsukasa Kusakizako / Tomohiro Nishizawa / Kazumasa Oda / Ryuichiro Ishitani / Takeshi Yokoyama / Takanori Nakane / Mikako Shirouzu / Hitoshi Endou / Shushi Nagamori / Yoshikatsu Kanai / Osamu Nureki / ![]() ![]() ![]() Abstract: The L-type amino acid transporter 1 (LAT1 or SLC7A5) transports large neutral amino acids across the membrane and is crucial for brain drug delivery and tumor growth. LAT1 forms a disulfide-linked ...The L-type amino acid transporter 1 (LAT1 or SLC7A5) transports large neutral amino acids across the membrane and is crucial for brain drug delivery and tumor growth. LAT1 forms a disulfide-linked heterodimer with CD98 heavy chain (CD98hc, 4F2hc or SLC3A2), but the mechanism of assembly and amino acid transport are poorly understood. Here we report the cryo-EM structure of the human LAT1-CD98hc heterodimer at 3.3-Å resolution. LAT1 features a canonical Leu T-fold and exhibits an unusual loop structure on transmembrane helix 6, creating an extended cavity that might accommodate bulky amino acids and drugs. CD98hc engages with LAT1 through the extracellular, transmembrane and putative cholesterol-mediated interactions. We also show that two anti-CD98 antibodies recognize distinct, multiple epitopes on CD98hc but not its glycans, explaining their robust reactivities. These results reveal the principles of glycoprotein-solute carrier assembly and provide templates for improving preclinical drugs and antibodies targeting LAT1 or CD98hc. | ||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 20.4 KB 20.4 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 6.8 KB | Display | ![]() |
Images | ![]() | 145.5 KB | ||
Masks | ![]() | 26.2 MB | ![]() | |
Others | ![]() ![]() | 20 MB 20 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6jmrMC ![]() 9849C ![]() 6jmqC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data #1: Unaligned multi-frame micrographs [micrographs - multiframe]) |
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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 | Masked, sharpend map calculated with the mask covering CD98hc-ED and two Fabs. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.49 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | ![]() | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: Half map 1 used for FSC calculation.
File | emd_9850_half_map_1.map | ||||||||||||
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Annotation | Half map 1 used for FSC calculation. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 2 used for FSC calculation.
File | emd_9850_half_map_2.map | ||||||||||||
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Annotation | Half map 2 used for FSC calculation. | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : CD98hc extracellular domain bound to MEM-108 Fab and HBJ127 Fab
Entire | Name: CD98hc extracellular domain bound to MEM-108 Fab and HBJ127 Fab |
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Components |
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-Supramolecule #1: CD98hc extracellular domain bound to MEM-108 Fab and HBJ127 Fab
Supramolecule | Name: CD98hc extracellular domain bound to MEM-108 Fab and HBJ127 Fab type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: ![]() |
Molecular weight | Experimental: 225 kDa/nm |
-Macromolecule #1: Antibody
Macromolecule | Name: Antibody / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 23.831834 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QVKLLESGPG LVQPSQSLSI TCTVSGFSLT TYGIHWVRQP PGKGLEWLGV IWSNGRIDYN AAFISRLSIT KDNSKSQVFF KMNSLQDDD TAIYYCARNV YDSLTWFTYW GQGTLVTVSA AKTTPPSVYP LAPGSAAQTN SMVTLGCLVK GYFPEPVTVT W NSGSLSSG ...String: QVKLLESGPG LVQPSQSLSI TCTVSGFSLT TYGIHWVRQP PGKGLEWLGV IWSNGRIDYN AAFISRLSIT KDNSKSQVFF KMNSLQDDD TAIYYCARNV YDSLTWFTYW GQGTLVTVSA AKTTPPSVYP LAPGSAAQTN SMVTLGCLVK GYFPEPVTVT W NSGSLSSG VHTFPAVLQS DLYTLSSSVT VPSSTWPSET VTCNVAHPAS STKVDKKIVP RD |
-Macromolecule #2: Antibody
Macromolecule | Name: Antibody / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 24.11467 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DIQMTQSPSS LAVSVGEKVT MTCKSSQSLL YSSNQKNYLA WYQQKPGQSP KLLIFWASTR ESGVPDRFTG SGSGTDFPLT ISSVKAEDL AVYFCQQYTS YPTFGGGTKL EIKRADAAPT VSIFPPSSEQ LTSGGASVVC FLNNFYPKDI NVKWKIDGSE R QNGVLNSW ...String: DIQMTQSPSS LAVSVGEKVT MTCKSSQSLL YSSNQKNYLA WYQQKPGQSP KLLIFWASTR ESGVPDRFTG SGSGTDFPLT ISSVKAEDL AVYFCQQYTS YPTFGGGTKL EIKRADAAPT VSIFPPSSEQ LTSGGASVVC FLNNFYPKDI NVKWKIDGSE R QNGVLNSW TDQDSKDSTY SMSSTLTLTK DEYERHNSYT CEATHKTSTS PIVKSFNRNE |
-Macromolecule #3: 4F2 cell-surface antigen heavy chain
Macromolecule | Name: 4F2 cell-surface antigen heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 68.069625 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: GSELQPPEAS IAVVSIPRQL PGSHSEAGVQ GLSAGDDSEL GSHCVAQTGL ELLASGDPLP SASQNAEMIE TGSDCVTQAG LQLLASSDP PALASKNAEV TGTMSQDTEV DMKEVELNEL EPEKQPMNAA SGAAMSLAGA EKNGLVKIKV AEDEAEAAAA A KFTGLSKE ...String: GSELQPPEAS IAVVSIPRQL PGSHSEAGVQ GLSAGDDSEL GSHCVAQTGL ELLASGDPLP SASQNAEMIE TGSDCVTQAG LQLLASSDP PALASKNAEV TGTMSQDTEV DMKEVELNEL EPEKQPMNAA SGAAMSLAGA EKNGLVKIKV AEDEAEAAAA A KFTGLSKE ELLKVAGSPG WVRTRWALLL LFWLGWLGML AGAVVIIVRA PRCRELPAQK WWHTGALYRI GDLQAFQGHG AG NLAGLKG RLDYLSSLKV KGLVLGPIHK NQKDDVAQTD LLQIDPNFGS KEDFDSLLQS AKKKSIRVIL DLTPNYRGEN SWF STQVDT VATKVKDALE FWLQAGVDGF QVRDIENLKD ASSFLAEWQN ITKGFSEDRL LIAGTNSSDL QQILSLLESN KDLL LTSSY LSDSGSTGEH TKSLVTQYLN ATGNRWCSWS LSQARLLTSF LPAQLLRLYQ LMLFTLPGTP VFSYGDEIGL DAAAL PGQP MEAPVMLWDE SSFPDIPGAV SANMTVKGQS EDPGSLLSLF RRLSDQRSKE RSLLHGDFHA FSAGPGLFSY IRHWDQ NER FLVVLNFGDV GLSAGLQASD LPASASLPAK ADLLLSTQPG REEGSPLELE RLKLEPHEGL LLRFPYAA |
-Macromolecule #4: Antibody
Macromolecule | Name: Antibody / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 22.577857 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QVQLKESGPG LVAPSQSLSI TCTVSGFPLT (UNK)(UNK)(UNK)(UNK)(UNK)WVRQP PGKGLEWLG(UNK) (UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)RLSI SKDNSK SQV FLKMNSLQTD ...String: QVQLKESGPG LVAPSQSLSI TCTVSGFPLT (UNK)(UNK)(UNK)(UNK)(UNK)WVRQP PGKGLEWLG(UNK) (UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)RLSI SKDNSK SQV FLKMNSLQTD DTARYYCAR(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)W GQGTSVT VS SAKTTPPSVY PLAPGS(UNK)(UNK)(UNK)(UNK) (UNK)SMVTLGCLV KGYFPEPVTV TWNSGSLSSG VHTFPAVL Q SDLYTLSSSV TVPSSTWPSE TVTCNVAHPA SSTKVDKKIV PRD |
-Macromolecule #5: Antibody
Macromolecule | Name: Antibody / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 23.227152 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DIVMSQSPSS LVVSVGEKVT MSC(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK) (UNK)WYQQKPGQS PKLLIY(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) GVPDRF TGSGSGTDFT ...String: DIVMSQSPSS LVVSVGEKVT MSC(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK) (UNK)WYQQKPGQS PKLLIY(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) GVPDRF TGSGSGTDFT LTISSVKAED LAVYYC(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)FGG G TKLEIKRADA APTVSIFPPS SEQLTSGGAS VVCFLNNFYP KDINVKWKID GSERQNGVLN SWTDQDSKDS TYSMSSTLT LTKDEYERHN SYTCEATHKT STSPIVKSFN RNE |
-Macromolecule #6: N-ACETYL-D-GLUCOSAMINE
Macromolecule | Name: N-ACETYL-D-GLUCOSAMINE / type: ligand / ID: 6 / Number of copies: 5 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
-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 TECNAI ARCTICA |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 50.2 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |