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Open data
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Basic information
Entry | Database: PDB / ID: 7wmv | ||||||||||||
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Title | Structure of human SGLT1-MAP17 complex bound with LX2761 | ||||||||||||
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![]() | PROTEIN TRANSPORT / glucose transporter / SGLT / sodium glucose transporter / membrane protein | ||||||||||||
Function / homology | ![]() myo-inositol:sodium symporter activity / pentose transmembrane transporter activity / fucose transmembrane transporter activity / galactose:sodium symporter activity / pentose transmembrane transport / intestinal hexose absorption / Defective SLC5A1 causes congenital glucose/galactose malabsorption (GGM) / Intestinal hexose absorption / fucose transmembrane transport / myo-inositol transport ...myo-inositol:sodium symporter activity / pentose transmembrane transporter activity / fucose transmembrane transporter activity / galactose:sodium symporter activity / pentose transmembrane transport / intestinal hexose absorption / Defective SLC5A1 causes congenital glucose/galactose malabsorption (GGM) / Intestinal hexose absorption / fucose transmembrane transport / myo-inositol transport / intestinal D-glucose absorption / galactose transmembrane transporter activity / alpha-glucoside transport / alpha-glucoside transmembrane transporter activity / glucose:sodium symporter activity / galactose transmembrane transport / water transmembrane transporter activity / D-glucose transmembrane transporter activity / Cellular hexose transport / glucose transmembrane transporter activity / renal glucose absorption / glucose import across plasma membrane / glucose transmembrane transport / transepithelial water transport / intracellular organelle / sodium ion import across plasma membrane / sodium ion transport / intracellular vesicle / transport across blood-brain barrier / : / brush border membrane / early endosome / apical plasma membrane / perinuclear region of cytoplasm / extracellular exosome / membrane / plasma membrane Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||||||||
![]() | Chen, L. / Niu, Y. / Cui, W. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural mechanism of SGLT1 inhibitors. Authors: Yange Niu / Wenhao Cui / Rui Liu / Sanshan Wang / Han Ke / Xiaoguang Lei / Lei Chen / ![]() Abstract: Sodium glucose co-transporters (SGLT) harness the electrochemical gradient of sodium to drive the uphill transport of glucose across the plasma membrane. Human SGLT1 (hSGLT1) plays a key role in ...Sodium glucose co-transporters (SGLT) harness the electrochemical gradient of sodium to drive the uphill transport of glucose across the plasma membrane. Human SGLT1 (hSGLT1) plays a key role in sugar uptake from food and its inhibitors show promise in the treatment of several diseases. However, the inhibition mechanism for hSGLT1 remains elusive. Here, we present the cryo-EM structure of the hSGLT1-MAP17 hetero-dimeric complex in the presence of the high-affinity inhibitor LX2761. LX2761 locks the transporter in an outward-open conformation by wedging inside the substrate-binding site and the extracellular vestibule of hSGLT1. LX2761 blocks the putative water permeation pathway of hSGLT1. The structure also uncovers the conformational changes of hSGLT1 during transitions from outward-open to inward-open states. | ||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 130.6 KB | Display | ![]() |
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PDB format | ![]() | 102.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.3 MB | Display | ![]() |
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Full document | ![]() | 1.3 MB | Display | |
Data in XML | ![]() | 31.2 KB | Display | |
Data in CIF | ![]() | 43.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 32617MC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 73557.703 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Protein | Mass: 12265.092 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#3: Chemical | ChemComp-1YI / |
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 |
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Sample preparation
Component | Name: human SGLT1-MAP17 complex / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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 / Nominal defocus max: 1800 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
EM software | Name: cryoSPARC / Version: v3.1.0 / Category: 3D reconstruction |
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CTF correction | Type: NONE |
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 12133 / Symmetry type: POINT |