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Yorodumi- EMDB-16111: Map of Human Urea Transporter UT-A Collected with 0 and 30 Degree... -
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-Basic information
Entry | Database: EMDB / ID: EMD-16111 | |||||||||
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Title | Map of Human Urea Transporter UT-A Collected with 0 and 30 Degree Tilts | |||||||||
Map data | ||||||||||
Sample |
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Keywords | SLC14A2 / UT2 / UT-A / Urea Transporter / Inhibitor / Solute Carrier / TRANSPORT PROTEIN | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
Authors | Chi G / Pike ACW / Maclean EM / Bohstedt T / Wang D / Mckinley G / Fernandez-Cid A / Mukhopadhyay SMM / Burgess-Brown NA / Edwards A ...Chi G / Pike ACW / Maclean EM / Bohstedt T / Wang D / Mckinley G / Fernandez-Cid A / Mukhopadhyay SMM / Burgess-Brown NA / Edwards A / Arrowsmith C / Bountra C / Duerr KL | |||||||||
Funding support | United Kingdom, European Union, 2 items
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Citation | Journal: Sci Adv / Year: 2023 Title: Structural characterization of human urea transporters UT-A and UT-B and their inhibition. Authors: Gamma Chi / Larissa Dietz / Haiping Tang / Matthew Snee / Andreea Scacioc / Dong Wang / Gavin Mckinley / Shubhashish M M Mukhopadhyay / Ashley C W Pike / Rod Chalk / Nicola A Burgess-Brown / ...Authors: Gamma Chi / Larissa Dietz / Haiping Tang / Matthew Snee / Andreea Scacioc / Dong Wang / Gavin Mckinley / Shubhashish M M Mukhopadhyay / Ashley C W Pike / Rod Chalk / Nicola A Burgess-Brown / Jean-Pierre Timmermans / Wouter van Putte / Carol V Robinson / Katharina L Dürr / Abstract: In this study, we present the structures of human urea transporters UT-A and UT-B to characterize them at molecular level and to detail the mechanism of UT-B inhibition by its selective inhibitor, ...In this study, we present the structures of human urea transporters UT-A and UT-B to characterize them at molecular level and to detail the mechanism of UT-B inhibition by its selective inhibitor, UTB-14. High-resolution structures of both transporters establish the structural basis for the inhibitor's selectivity to UT-B, and the identification of multiple binding sites for the inhibitor will aid with the development of drug lead molecules targeting both transporters. Our study also discovers phospholipids associating with the urea transporters by combining structural observations, native MS, and lipidomics analysis. These insights improve our understanding of urea transporter function at a molecular level and provide a blueprint for a structure-guided design of therapeutics targeting these transporters. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_16111.map.gz | 97 MB | EMDB map data format | |
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Header (meta data) | emd-16111-v30.xml emd-16111.xml | 16.9 KB 16.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_16111_fsc.xml | 15.3 KB | Display | FSC data file |
Images | emd_16111.png | 125.3 KB | ||
Masks | emd_16111_msk_1.map | 103 MB | Mask map | |
Filedesc metadata | emd-16111.cif.gz | 5.8 KB | ||
Others | emd_16111_half_map_1.map.gz emd_16111_half_map_2.map.gz | 95.5 MB 95.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-16111 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16111 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_16111.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.82 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_16111_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_16111_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_16111_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Trimer-like complex of Human UT-A
Entire | Name: Trimer-like complex of Human UT-A |
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Components |
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-Supramolecule #1: Trimer-like complex of Human UT-A
Supramolecule | Name: Trimer-like complex of Human UT-A / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 120 KDa |
-Macromolecule #1: Human Urea Transporter UT-A
Macromolecule | Name: Human Urea Transporter UT-A / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MSDPHSSPLL PEPLSSRYKL YEAEFTSPSW PSTSPDTHPA LPLLEMPEEK DLRSSNEDSH IVKIEKLNER SKRKDDGVAH RDSAGQRCIC LSKAVGYLTG DMKEYRIWLK DKHLALQFID WVLRGTAQVM FINNPLSGLI IFIGLLIQNP WWTITGGLGT VVSTLTALAL ...String: MSDPHSSPLL PEPLSSRYKL YEAEFTSPSW PSTSPDTHPA LPLLEMPEEK DLRSSNEDSH IVKIEKLNER SKRKDDGVAH RDSAGQRCIC LSKAVGYLTG DMKEYRIWLK DKHLALQFID WVLRGTAQVM FINNPLSGLI IFIGLLIQNP WWTITGGLGT VVSTLTALAL GQDRSAIASG LHGYNGMLVG LLMAVFSEKL DYYWWLLFPV TFTAMSCPVL SSALNSIFSK WDLPVFTLPF NIAVTLYLAA TGHYNLFFPT TLVEPVSSVP NITWTEMEMP LLLQAIPVGV GQVYGCDNPW TGGVFLVALF ISSPLICLHA AIGSIVGLLA ALSVATPFET IYTGLWSYNC VLSCIAIGGM FYALTWQTHL LALICALFCA YMEAAISNIM SVVGVPPGTW AFCLATIIFL LLTTNNPAIF RLPLSKVTYP EANRIYYLTV KSGEEEKAPS GGGGEHPPTA GPKVEEGSEA VLSKHRSVFH IEWSSIRRRS KVFGKGEHQE RQNKDPFPYR YRKPTVELLD LDTMEESSEI KVETNISKTS WIRSSMAASG KRVSKALSYI TGEMKECGEG LKDKSPVFQF FDWVLRGTSQ VMFVNNPLSG ILIILGLFIQ NPWWAISGCL GTIMSTLTAL ILSQDKSAIA AGFHGYNGVL VGLLMAVFSD KGDYYWWLLL PVIIMSMSCP ILSSALGTIF SKWDLPVFTL PFNITVTLYL AATGHYNLFF PTTLLQPASA MPNITWSEVQ VPLLLRAIPV GIGQVYGCDN PWTGGIFLIA LFISSPLICL HAAIGSTMGM LAALTIATPF DSIYFGLCGF NSTLACIAIG GMFYVITWQT HLLAIACALF AAYLGAALAN MLSVFGLPPC TWPFCLSALT FLLLTTNNPA IYKLPLSKVT YPEANRIYYL SQEAENLYFQ |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil | |||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 1.0 µm |
Details | Some movies were collected with 0 degree tilt. Some were collected with 30 degree tilt. Collection settings were otherwise identical for the two set ups. |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 52.63 e/Å2 Details: Some movies were collected with 0 degree tilt. Some were collected with 30 degree tilt. Collection settings were otherwise identical for the two set ups. |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |