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Yorodumi- EMDB-37492: human glycine transporter 1 in complex with glycine in occluded c... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-37492 | |||||||||
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Title | human glycine transporter 1 in complex with glycine in occluded conformation | |||||||||
Map data | ||||||||||
Sample |
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Keywords | GlyT1 / glycine / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information glycine:sodium symporter activity / regulation of synaptic transmission, glycinergic / glycine transmembrane transporter activity / negative regulation of NMDA glutamate receptor activity / positive regulation of heme biosynthetic process / glycine import across plasma membrane / glycine transport / positive regulation of hemoglobin biosynthetic process / dense core granule / synaptic transmission, glycinergic ...glycine:sodium symporter activity / regulation of synaptic transmission, glycinergic / glycine transmembrane transporter activity / negative regulation of NMDA glutamate receptor activity / positive regulation of heme biosynthetic process / glycine import across plasma membrane / glycine transport / positive regulation of hemoglobin biosynthetic process / dense core granule / synaptic transmission, glycinergic / Na+/Cl- dependent neurotransmitter transporters / neurotransmitter transport / parallel fiber to Purkinje cell synapse / transport across blood-brain barrier / lateral plasma membrane / sodium ion transmembrane transport / hippocampal mossy fiber to CA3 synapse / basal plasma membrane / synaptic vesicle membrane / presynaptic membrane / basolateral plasma membrane / postsynaptic membrane / postsynaptic density / endosome / apical plasma membrane / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.58 Å | |||||||||
Authors | Wei Y / Zhao Y | |||||||||
Funding support | China, 1 items
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Citation | Journal: Cell / Year: 2024 Title: Transport mechanism and pharmacology of the human GlyT1. Authors: Yiqing Wei / Renjie Li / Yufei Meng / Tuo Hu / Jun Zhao / Yiwei Gao / Qinru Bai / Na Li / Yan Zhao / Abstract: The glycine transporter 1 (GlyT1) plays a crucial role in the regulation of both inhibitory and excitatory neurotransmission by removing glycine from the synaptic cleft. Given its close association ...The glycine transporter 1 (GlyT1) plays a crucial role in the regulation of both inhibitory and excitatory neurotransmission by removing glycine from the synaptic cleft. Given its close association with glutamate/glycine co-activated NMDA receptors (NMDARs), GlyT1 has emerged as a central target for the treatment of schizophrenia, which is often linked to hypofunctional NMDARs. Here, we report the cryo-EM structures of GlyT1 bound with substrate glycine and drugs ALX-5407, SSR504734, and PF-03463275. These structures, captured at three fundamental states of the transport cycle-outward-facing, occluded, and inward-facing-enable us to illustrate a comprehensive blueprint of the conformational change associated with glycine reuptake. Additionally, we identified three specific pockets accommodating drugs, providing clear insights into the structural basis of their inhibitory mechanism and selectivity. Collectively, these structures offer significant insights into the transport mechanism and recognition of substrate and anti-schizophrenia drugs, thus providing a platform to design small molecules to treat schizophrenia. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_37492.map.gz | 117.8 MB | EMDB map data format | |
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Header (meta data) | emd-37492-v30.xml emd-37492.xml | 14.8 KB 14.8 KB | Display Display | EMDB header |
Images | emd_37492.png | 40.3 KB | ||
Filedesc metadata | emd-37492.cif.gz | 5.5 KB | ||
Others | emd_37492_half_map_1.map.gz emd_37492_half_map_2.map.gz | 115.9 MB 115.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-37492 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-37492 | HTTPS FTP |
-Validation report
Summary document | emd_37492_validation.pdf.gz | 796 KB | Display | EMDB validaton report |
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Full document | emd_37492_full_validation.pdf.gz | 795.5 KB | Display | |
Data in XML | emd_37492_validation.xml.gz | 13.9 KB | Display | |
Data in CIF | emd_37492_validation.cif.gz | 16.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37492 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37492 | HTTPS FTP |
-Related structure data
Related structure data | 8wfiMC 8wfjC 8wfkC 8wflC 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_37492.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.85 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_37492_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_37492_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : human glycine transporter 1 (GlyT1)
Entire | Name: human glycine transporter 1 (GlyT1) |
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Components |
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-Supramolecule #1: human glycine transporter 1 (GlyT1)
Supramolecule | Name: human glycine transporter 1 (GlyT1) / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Isoform GlyT-1B of Sodium- and chloride-dependent glycine transpo...
Macromolecule | Name: Isoform GlyT-1B of Sodium- and chloride-dependent glycine 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: 63.769484 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: RGNWGNQIEF VLTSVGYAVG LGNVWRFPYL CYRNAGGAFM FPYFIMLIFC GIPLFFMELS FGQFASQGCL GVWRISPMFK GVGYGMMVV STYIGIYYNV VICIAFYYFF SSMTHVLPWA YCNNPWNTHD CAGVLDASNL TNGSRPAALP SNLSHLLNHS L QRTSPSEE ...String: RGNWGNQIEF VLTSVGYAVG LGNVWRFPYL CYRNAGGAFM FPYFIMLIFC GIPLFFMELS FGQFASQGCL GVWRISPMFK GVGYGMMVV STYIGIYYNV VICIAFYYFF SSMTHVLPWA YCNNPWNTHD CAGVLDASNL TNGSRPAALP SNLSHLLNHS L QRTSPSEE YWRLYVLKLS DDIGNFGEVR LPLLGCLGVS WLVVFLCLIR GVKSSGKVVY FTATFPYVVL TILFVRGVTL EG AFDGIMY YLTPQWDKIL AAKVWGDAAS QIFYSLGCAW GGLITMASYN KFHNNCYRDS VIISITNCAT SVYAGFVIFS ILG FMANHL GVDVSRVADH GPGLAFVAYP EALTLLPISP LWSLLFFFML ILLGLGTQFC LLETLVTAIV DEVGNEWILQ KKTY VTLGV AVAGFLLGIP LTSQAGIYWL LLMDNYAASF SLVVISCIMC VAIMYIYGHR NYFQDIQMML GFPPPLFFQI CWRFV SPAI IFFILVFTVI QYPITAYNHY QYPGWAVAIG FLMALSSVLC IPLYAMFRLC RTDGADLLQR LKNATKPSRD WGPALL EHR TGRYAP UniProtKB: Sodium- and chloride-dependent glycine transporter 1 |
-Macromolecule #2: GLYCINE
Macromolecule | Name: GLYCINE / type: ligand / ID: 2 / Number of copies: 1 / Formula: GLY |
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Molecular weight | Theoretical: 75.067 Da |
Chemical component information | ChemComp-GLY: |
-Macromolecule #3: CHLORIDE ION
Macromolecule | Name: CHLORIDE ION / type: ligand / ID: 3 / Number of copies: 1 / Formula: CL |
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Molecular weight | Theoretical: 35.453 Da |
-Macromolecule #4: SODIUM ION
Macromolecule | Name: SODIUM ION / type: ligand / ID: 4 / Number of copies: 2 |
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Molecular weight | Theoretical: 22.99 Da |
-Macromolecule #5: water
Macromolecule | Name: water / type: ligand / ID: 5 / Number of copies: 37 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.58 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 129157 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |