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- PDB-7ty6: Cryo-EM structure of human Anion Exchanger 1 bound to 4,4'-Diisot... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7ty6 | ||||||||||||
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Title | Cryo-EM structure of human Anion Exchanger 1 bound to 4,4'-Diisothiocyanatodihydrostilbene-2,2'-Disulfonic Acid (H2DIDS) | ||||||||||||
![]() | Band 3 anion transport protein![]() | ||||||||||||
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Function / homology | ![]() pH elevation / Defective SLC4A1 causes hereditary spherocytosis type 4 (HSP4), distal renal tubular acidosis (dRTA) and dRTA with hemolytic anemia (dRTA-HA) / negative regulation of urine volume / Bicarbonate transporters / intracellular monoatomic ion homeostasis / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() | ||||||||||||
Method | ![]() ![]() ![]() | ||||||||||||
![]() | Capper, M.J. / Mathiharan, Y.K. / Yang, S. / Stone, A.C. / Wacker, D. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Substrate binding and inhibition of the anion exchanger 1 transporter. Authors: Michael J Capper / Shifan Yang / Alexander C Stone / Sezen Vatansever / Gregory Zilberg / Yamuna Kalyani Mathiharan / Raul Habib / Keino Hutchinson / Yihan Zhao / Avner Schlessinger / Mihaly ...Authors: Michael J Capper / Shifan Yang / Alexander C Stone / Sezen Vatansever / Gregory Zilberg / Yamuna Kalyani Mathiharan / Raul Habib / Keino Hutchinson / Yihan Zhao / Avner Schlessinger / Mihaly Mezei / Roman Osman / Bin Zhang / Daniel Wacker / ![]() Abstract: Anion exchanger 1 (AE1), a member of the solute carrier (SLC) family, is the primary bicarbonate transporter in erythrocytes, regulating pH levels and CO transport between lungs and tissues. Previous ...Anion exchanger 1 (AE1), a member of the solute carrier (SLC) family, is the primary bicarbonate transporter in erythrocytes, regulating pH levels and CO transport between lungs and tissues. Previous studies characterized its role in erythrocyte structure and provided insight into transport regulation. However, key questions remain regarding substrate binding and transport, mechanisms of drug inhibition and modulation by membrane components. Here we present seven cryo-EM structures in apo, bicarbonate-bound and inhibitor-bound states. These, combined with uptake and computational studies, reveal important molecular features of substrate recognition and transport, and illuminate sterol binding sites, to elucidate distinct inhibitory mechanisms of research chemicals and prescription drugs. We further probe the substrate binding site via structure-based ligand screening, identifying an AE1 inhibitor. Together, our findings provide insight into mechanisms of solute carrier transport and inhibition. | ||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 242.9 KB | Display | ![]() |
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PDB format | ![]() | 182.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 26167MC ![]() 7ty4C ![]() 7ty7C ![]() 7ty8C ![]() 7tyaC ![]() 8t6uC ![]() 8t6vC 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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1 |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: 1 / Ens-ID: 1 / Beg auth comp-ID: ASP / Beg label comp-ID: ASP / End auth comp-ID: ALA / End label comp-ID: ALA / Auth seq-ID: 369 - 891 / Label seq-ID: 369 - 891
NCS ensembles : (Details: Global NCS restraints between domains: 1 2) NCS oper:
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Components
-Protein / Sugars , 2 types, 4 molecules AB
#1: Protein | ![]() Mass: 101883.859 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() #2: Polysaccharide | ![]() |
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-Non-polymers , 4 types, 76 molecules ![](data/chem/img/CLR.gif)
![](data/chem/img/PC1.gif)
![](data/chem/img/4DS.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/PC1.gif)
![](data/chem/img/4DS.gif)
![](data/chem/img/HOH.gif)
#3: Chemical | ChemComp-CLR / ![]() #4: Chemical | ![]() #5: Chemical | ![]() #6: Water | ChemComp-HOH / | ![]() |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: Dimeric anion exchanger 1 (SLC4A1) / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | ||||||||||||||||||||||||
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Molecular weight | Value: 0.203 MDa / Experimental value: NO | ||||||||||||||||||||||||
Source (natural) | Organism: ![]() ![]() | ||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() ![]() ![]() | ||||||||||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 4.1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() Details: The sample was monodisperse following gel filtration and immediately concentrated for grid preparation | ||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||||||
Vitrification![]() | Instrument: LEICA EM GP / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 285 K Details: Blot force 3 for 3-5 seconds was used and subsequent grids were screened for ice thickness prior to data collection |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() ![]() |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 51.85 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 11020 |
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Processing
Software | Name: REFMAC / Version: 5.8.0267 / Classification: refinement | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 2460255 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry![]() ![]() | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 2.98 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 267008 / Num. of class averages: 1 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Space: RECIPROCAL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 4YZF Accession code: 4YZF / Source name: PDB / Type: experimental model | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement | Resolution: 2.98→120.512 Å / Cor.coef. Fo:Fc: 0.9 / WRfactor Rwork: 0.323 / Average fsc overall: 0.8674 / Average fsc work: 0.8674 / ESU R: 0.384 Details: Hydrogens have been added in their riding positions
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Solvent computation | Solvent model: BABINET MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 92.332 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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