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Yorodumi- PDB-8wny: Cryo EM map of SLC7A10-SLC3A2 complex in the D-serine bound state -
+Open data
-Basic information
Entry | Database: PDB / ID: 8wny | ||||||
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Title | Cryo EM map of SLC7A10-SLC3A2 complex in the D-serine bound state | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / SLC7A10 / SLC3A2 | ||||||
Function / homology | Function and homology information D-serine transmembrane transport / positive regulation of synaptic transmission, glycinergic / D-alanine transmembrane transport / L-amino acid transmembrane transporter activity / amino acid transmembrane transport / glycine transport / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / neutral L-amino acid secondary active transmembrane transporter activity / aromatic amino acid transmembrane transporter activity / tyrosine transport ...D-serine transmembrane transport / positive regulation of synaptic transmission, glycinergic / D-alanine transmembrane transport / L-amino acid transmembrane transporter activity / amino acid transmembrane transport / glycine transport / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / neutral L-amino acid secondary active transmembrane transporter activity / aromatic amino acid transmembrane transporter activity / tyrosine transport / apical pole of neuron / L-histidine transport / amino acid transport complex / negative regulation of brown fat cell differentiation / L-serine transmembrane transporter activity / methionine transport / L-leucine import across plasma membrane / L-alanine transmembrane transporter activity / L-leucine transmembrane transporter activity / L-alanine import across plasma membrane / isoleucine transport / phenylalanine transport / valine transport / L-leucine transport / calcium:sodium antiporter activity / 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 / 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 | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||
Authors | Li, Y.N. / Guo, Y.Y. / Dai, L. / Yan, R.H. | ||||||
Funding support | 1items
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Citation | Journal: Nat Commun / Year: 2024 Title: Cryo-EM structure of the human Asc-1 transporter complex. Authors: Yaning Li / Yingying Guo / Angelika Bröer / Lu Dai / Stefan Brӧer / Renhong Yan / Abstract: The Alanine-Serine-Cysteine transporter 1 (Asc-1 or SLC7A10) forms a crucial heterodimeric transporter complex with 4F2hc (SLC3A2) through a covalent disulfide bridge. This complex enables the sodium- ...The Alanine-Serine-Cysteine transporter 1 (Asc-1 or SLC7A10) forms a crucial heterodimeric transporter complex with 4F2hc (SLC3A2) through a covalent disulfide bridge. This complex enables the sodium-independent transport of small neutral amino acids, including L-Alanine (L-Ala), Glycine (Gly), and D-Serine (D-Ser), within the central nervous system (CNS). D-Ser and Gly are two key endogenous glutamate co-agonists that activate N-methyl-d-aspartate (NMDA) receptors by binding to the allosteric site. Mice deficient in Asc-1 display severe symptoms such as tremors, ataxia, and seizures, leading to early postnatal death. Despite its physiological importance, the functional mechanism of the Asc-1-4F2hc complex has remained elusive. Here, we present cryo-electron microscopy (cryo-EM) structures of the human Asc-1-4F2hc complex in its apo state, D-Ser bound state, and L-Ala bound state, resolved at 3.6 Å, 3.5 Å, and 3.4 Å, respectively. Through detailed structural analysis and transport assays, we uncover a comprehensive alternating access mechanism that underlies conformational changes in the complex. In summary, our findings reveal the architecture of the Asc-1 and 4F2hc complex and provide valuable insights into substrate recognition and the functional cycle of this essential transporter complex. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8wny.cif.gz | 195.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8wny.ent.gz | 148.8 KB | Display | PDB format |
PDBx/mmJSON format | 8wny.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8wny_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 8wny_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 8wny_validation.xml.gz | 36.5 KB | Display | |
Data in CIF | 8wny_validation.cif.gz | 53.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wn/8wny ftp://data.pdbj.org/pub/pdb/validation_reports/wn/8wny | HTTPS FTP |
-Related structure data
Related structure data | 37675MC 8wnsC 8wntC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 68164.680 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 | ||||
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#2: Protein | Mass: 56837.504 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SLC7A10, ASC1 / Production host: Homo sapiens (human) / References: UniProt: Q9NS82 | ||||
#3: Sugar | ChemComp-NAG / #4: Chemical | ChemComp-DSN / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: 4F2hc-ASC-1 complex / Type: COMPLEX / Entity ID: #1-#2 / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
EM software | Name: PHENIX / Version: 1.20.1_4487: / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 300000 / Symmetry type: POINT | ||||||||||||||||||||||||
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