+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-25195 | |||||||||
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Title | CryoEM structure of SMCT1 | |||||||||
Map data | sodium monocarboxylate cotransporter | |||||||||
Sample |
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Function / homology | Function and homology information propionate transmembrane transporter activity / propanoate transmembrane transport / short-chain fatty acid transmembrane transport / passive transmembrane transporter activity / monocarboxylate:sodium symporter activity / Organic anion transporters / organic acid:sodium symporter activity / monocarboxylic acid transmembrane transporter activity / lactate transmembrane transporter activity / NAD biosynthesis via nicotinamide riboside salvage pathway ...propionate transmembrane transporter activity / propanoate transmembrane transport / short-chain fatty acid transmembrane transport / passive transmembrane transporter activity / monocarboxylate:sodium symporter activity / Organic anion transporters / organic acid:sodium symporter activity / monocarboxylic acid transmembrane transporter activity / lactate transmembrane transporter activity / NAD biosynthesis via nicotinamide riboside salvage pathway / Nicotinamide salvaging / symporter activity / sodium ion transport / monoatomic ion transport / membrane => GO:0016020 / apical plasma membrane / apoptotic process / extracellular exosome / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / synthetic construct (others) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Qu Q / Han L / Panova O / Feng L / Skiniotis G | |||||||||
Funding support | 1 items
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Citation | Journal: Nature / Year: 2022 Title: Structure and mechanism of the SGLT family of glucose transporters. Authors: Lei Han / Qianhui Qu / Deniz Aydin / Ouliana Panova / Michael J Robertson / Yan Xu / Ron O Dror / Georgios Skiniotis / Liang Feng / Abstract: Glucose is a primary energy source in living cells. The discovery in 1960s that a sodium gradient powers the active uptake of glucose in the intestine heralded the concept of a secondary active ...Glucose is a primary energy source in living cells. The discovery in 1960s that a sodium gradient powers the active uptake of glucose in the intestine heralded the concept of a secondary active transporter that can catalyse the movement of a substrate against an electrochemical gradient by harnessing energy from another coupled substrate. Subsequently, coupled Na/glucose transport was found to be mediated by sodium-glucose cotransporters (SGLTs). SGLTs are responsible for active glucose and galactose absorption in the intestine and for glucose reabsorption in the kidney, and are targeted by multiple drugs to treat diabetes. Several members within the SGLT family transport key metabolites other than glucose. Here we report cryo-electron microscopy structures of the prototypic human SGLT1 and a related monocarboxylate transporter SMCT1 from the same family. The structures, together with molecular dynamics simulations and functional studies, define the architecture of SGLTs, uncover the mechanism of substrate binding and selectivity, and shed light on water permeability of SGLT1. These results provide insights into the multifaceted functions of SGLTs. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_25195.map.gz | 21 MB | EMDB map data format | |
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Header (meta data) | emd-25195-v30.xml emd-25195.xml | 11.3 KB 11.3 KB | Display Display | EMDB header |
Images | emd_25195.png | 51.5 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-25195 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-25195 | HTTPS FTP |
-Related structure data
Related structure data | 7sl9MC 7sl8C 7slaC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_25195.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | sodium monocarboxylate cotransporter | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : SMCT1 and nanobody complex
Entire | Name: SMCT1 and nanobody complex |
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Components |
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-Supramolecule #1: SMCT1 and nanobody complex
Supramolecule | Name: SMCT1 and nanobody complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Sodium-coupled monocarboxylate transporter 1
Macromolecule | Name: Sodium-coupled monocarboxylate 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: 67.636219 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MDTPRGIGTF VVWDYVVFAG MLVISAAIGI YYAFAGGGQQ TSKDFLMGGR RMTAVPVALS LTASFMSAVT VLGTPSEVYR FGAIFSIFA FTYFFVVVIS AEVFLPVFYK LGITSTYEYL ELRFNKCVRL CGTVLFIVQT ILYTGIVIYA PALALNQVTG F DLWGAVVA ...String: MDTPRGIGTF VVWDYVVFAG MLVISAAIGI YYAFAGGGQQ TSKDFLMGGR RMTAVPVALS LTASFMSAVT VLGTPSEVYR FGAIFSIFA FTYFFVVVIS AEVFLPVFYK LGITSTYEYL ELRFNKCVRL CGTVLFIVQT ILYTGIVIYA PALALNQVTG F DLWGAVVA TGVVCTFYCT LGGLKAVIWT DVFQVGIMVA GFASVIIQAV VMQGGISTIL NDAYDGGRLN FWNFNPNPLQ RH TFWTIII GGTFTWTSIY GVNQSQVQRY ISCKSRFQAK LSLYINLVGL WAILTCSVFC GLALYSRYHD CDPWTAKKVS APD QLMPYL VLDILQDYPG LPGLFVACAY SGTLSTVSSS INALAAVTVE DLIKPYFRSL SERSLSWISQ GMSVVYGALC IGMA ALASL MGALLQAALS VFGMVGGPLM GLFALGILVP FANSIGALVG LMAGFAISLW VGIGAQIYPP LPERTLPLHL DIQGC NSTY NETNLMTTTE MPFTTSVFQI YNVQRTPLMD NWYSLSYLYF STVGTLVTLL VGILVSLSTG GRKQNLDPRY ILTKED FLS NFDIFKKKKH VLSYKSHPVE DGGTDNPAFN HIELNSDQSG KSNGTRLSNS LEVLFQ |
-Macromolecule #2: nanobody Nb2
Macromolecule | Name: nanobody Nb2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 14.441961 KDa |
Recombinant expression | Organism: Escherichia coli BL21(DE3) (bacteria) |
Sequence | String: MAQVQLQESG GGLVQAGGSL RLSCAASGNI STRAGMGWYR QAPGKEREFV ASINWGAITN YADSVKGRFT ISRDNAKNTV YLQMNSLKP EDTAVYYCAV EYKYGPQRSD TYYYWGQGTQ VTVSSHHHHH H |
-Macromolecule #3: butanoic acid
Macromolecule | Name: butanoic acid / type: ligand / ID: 3 / Number of copies: 1 / Formula: BUA |
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Molecular weight | Theoretical: 88.105 Da |
Chemical component information | ChemComp-BUA: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN 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 |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 56.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
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Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 173859 |