+Open data
-Basic information
Entry | Database: PDB / ID: 6jmr | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | CD98hc extracellular domain bound to HBJ127 Fab and MEM-108 Fab | ||||||||||||
Components |
| ||||||||||||
Keywords | MEMBRANE PROTEIN/IMMUNE SYSTEM / Transporter / Glycoprotein / Complex / MEMBRANE PROTEIN / MEMBRANE PROTEIN-IMMUNE SYSTEM complex | ||||||||||||
Function / homology | Function and homology information neutral L-amino acid secondary active transmembrane transporter activity / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / tyrosine transport / L-histidine transport / apical pole of neuron / aromatic amino acid transmembrane transporter activity / amino acid transport complex / methionine transport / : / L-leucine import across plasma membrane ...neutral L-amino acid secondary active transmembrane transporter activity / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / tyrosine transport / L-histidine transport / apical pole of neuron / aromatic amino acid transmembrane transporter activity / amino acid transport complex / methionine transport / : / 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 / proline transport / calcium:sodium antiporter activity / L-leucine transport / thyroid hormone transport / Amino acid transport across the plasma membrane / neutral L-amino acid transmembrane transporter activity / Tryptophan catabolism / exogenous protein binding / amino acid transport / anchoring junction / Basigin interactions / response to exogenous dsRNA / tryptophan transport / basal plasma membrane / calcium ion transport / melanosome / double-stranded RNA binding / 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 | Mus musculus (house mouse) Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.1 Å | ||||||||||||
Authors | Lee, Y. / Nishizawa, T. / Kusakizako, T. / Oda, K. / Ishitani, R. / Yokoyama, T. / Nakane, T. / Shirouzu, M. / Nureki, O. | ||||||||||||
Funding support | Japan, 3items
| ||||||||||||
Citation | Journal: Nat Struct Mol Biol / Year: 2019 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 |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6jmr.cif.gz | 232.6 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6jmr.ent.gz | 182.6 KB | Display | PDB format |
PDBx/mmJSON format | 6jmr.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jm/6jmr ftp://data.pdbj.org/pub/pdb/validation_reports/jm/6jmr | HTTPS FTP |
---|
-Related structure data
Related structure data | 9850MC 9849C 6jmqC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data | |
EM raw data | EMPIAR-10265 (Title: LAT1-CD98hc bound to HBJ127 Fab and MEM-108 Fab / Data size: 969.9 Data #1: Unaligned multi-frame micrographs [micrographs - multiframe]) |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Protein , 1 types, 1 molecules B
#3: Protein | Mass: 68069.625 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SLC3A2, MDU1 / Production host: Homo sapiens (human) / References: UniProt: P08195 |
---|
-Antibody , 4 types, 4 molecules EFCD
#1: Antibody | Mass: 23831.834 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Mus musculus (house mouse) |
---|---|
#2: Antibody | Mass: 24114.670 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Mus musculus (house mouse) |
#4: Antibody | Mass: 22577.857 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Mus musculus (house mouse) |
#5: Antibody | Mass: 23227.152 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Mus musculus (house mouse) |
-Sugars , 2 types, 4 molecules
#6: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
---|---|
#7: Sugar |
-Details
Sequence details | Authors do not know the actual sequences of chains C, D since the protein WAS derived from an ...Authors do not know the actual sequences of chains C, D since the protein WAS derived from an commercial antibody whose sequence is NOT available. |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: CD98hc extracellular domain bound to MEM-108 Fab and HBJ127 Fab Type: COMPLEX / Entity ID: #1-#5 / Source: MULTIPLE SOURCES |
---|---|
Molecular weight | Value: 225 kDa/nm / Experimental value: YES |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TECNAI ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 50.2 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 160553 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Stereochemistry target values: CDL v1.2 | ||||||||||||||||||||||||
Refine LS restraints |
|