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Open data
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Basic information
Entry | Database: PDB / ID: 7b00 | ||||||||||||||||||||||||
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Title | Human LAT2-4F2hc complex in the apo-state | ||||||||||||||||||||||||
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![]() | MEMBRANE PROTEIN / HATs / amino-acid / transporter / membrane / protein / heterodimer | ||||||||||||||||||||||||
Function / homology | ![]() proline transmembrane transport / glycine transmembrane transporter activity / organic cation transmembrane transporter activity / glycine transport / 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 ...proline transmembrane transport / glycine transmembrane transporter activity / organic cation transmembrane transporter activity / glycine transport / 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 / toxin transmembrane transporter activity / neutral amino acid transport / amino acid transmembrane transporter activity / Amino acid transport across the plasma membrane / neutral L-amino acid transmembrane transporter activity / Tryptophan catabolism / exogenous protein binding / anchoring junction / antiporter activity / Basigin interactions / microvillus membrane / amino acid transport / response to exogenous dsRNA / tryptophan transport / transport across blood-brain barrier / basal plasma membrane / peptide antigen binding / calcium ion transport / double-stranded RNA binding / melanosome / virus receptor activity / basolateral plasma membrane / carbohydrate metabolic process / cadherin binding / symbiont entry into host cell / protein heterodimerization activity / apical plasma membrane / lysosomal membrane / synapse / cell surface / protein homodimerization activity / RNA binding / extracellular exosome / nucleoplasm / membrane / plasma membrane Similarity search - Function | ||||||||||||||||||||||||
Biological species | ![]() | ||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.98 Å | ||||||||||||||||||||||||
![]() | Rodriguez, C.F. / Escudero-Bravo, P. / Garcia-Martin, C. / Boskovic, J. / Errasti-Murugarren, E. / Palacin, M. / Llorca, O. | ||||||||||||||||||||||||
Funding support | 7items
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![]() | ![]() Title: Structural basis for substrate specificity of heteromeric transporters of neutral amino acids. Authors: Carlos F Rodriguez / Paloma Escudero-Bravo / Lucía Díaz / Paola Bartoccioni / Carmen García-Martín / Joan G Gilabert / Jasminka Boskovic / Víctor Guallar / Ekaitz Errasti-Murugarren / ...Authors: Carlos F Rodriguez / Paloma Escudero-Bravo / Lucía Díaz / Paola Bartoccioni / Carmen García-Martín / Joan G Gilabert / Jasminka Boskovic / Víctor Guallar / Ekaitz Errasti-Murugarren / Oscar Llorca / Manuel Palacín / ![]() Abstract: Despite having similar structures, each member of the heteromeric amino acid transporter (HAT) family shows exquisite preference for the exchange of certain amino acids. Substrate specificity ...Despite having similar structures, each member of the heteromeric amino acid transporter (HAT) family shows exquisite preference for the exchange of certain amino acids. Substrate specificity determines the physiological function of each HAT and their role in human diseases. However, HAT transport preference for some amino acids over others is not yet fully understood. Using cryo-electron microscopy of apo human LAT2/CD98hc and a multidisciplinary approach, we elucidate key molecular determinants governing neutral amino acid specificity in HATs. A few residues in the substrate-binding pocket determine substrate preference. Here, we describe mutations that interconvert the substrate profiles of LAT2/CD98hc, LAT1/CD98hc, and Asc1/CD98hc. In addition, a region far from the substrate-binding pocket critically influences the conformation of the substrate-binding site and substrate preference. This region accumulates mutations that alter substrate specificity and cause hearing loss and cataracts. Here, we uncover molecular mechanisms governing substrate specificity within the HAT family of neutral amino acid transporters and provide the structural bases for mutations in LAT2/CD98hc that alter substrate specificity and that are associated with several pathologies. | ||||||||||||||||||||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 172.1 KB | Display | ![]() |
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PDB format | ![]() | 140.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 11952MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 58420.133 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||
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#2: Protein | Mass: 58003.652 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||
#3: 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 #4: Chemical | ChemComp-AJP / | Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Human LAT2 4F2hc complex in the apo state / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7 |
Specimen | Conc.: 1.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R0.6/1 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 297 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 1 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 |
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Processing
Software | Name: PHENIX / Version: 1.14_3260: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.98 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 176132 / Details: CTF refinement in cisTEM / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: BACKBONE TRACE / Space: REAL | ||||||||||||||||||||||||
Refine LS restraints |
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