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Yorodumi- PDB-6caa: CryoEM structure of human SLC4A4 sodium-coupled acid-base transpo... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6caa | ||||||||||||||||||||||||||||||||||||
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Title | CryoEM structure of human SLC4A4 sodium-coupled acid-base transporter NBCe1 | ||||||||||||||||||||||||||||||||||||
Components | Electrogenic sodium bicarbonate cotransporter 1 | ||||||||||||||||||||||||||||||||||||
Keywords | TRANSPORT PROTEIN / SLC4A4 / Electrogenic Sodium-Coupled Bicarbonate Cotransporters / NBCe1 | ||||||||||||||||||||||||||||||||||||
Function / homology | Function and homology information Defective SLC4A4 causes renal tubular acidosis, proximal, with ocular abnormalities and mental retardation (pRTA-OA) / sodium:bicarbonate symporter activity / monoatomic ion homeostasis / Bicarbonate transporters / sodium ion export across plasma membrane / solute:inorganic anion antiporter activity / symporter activity / bicarbonate transport / sodium ion transport / plasma membrane => GO:0005886 ...Defective SLC4A4 causes renal tubular acidosis, proximal, with ocular abnormalities and mental retardation (pRTA-OA) / sodium:bicarbonate symporter activity / monoatomic ion homeostasis / Bicarbonate transporters / sodium ion export across plasma membrane / solute:inorganic anion antiporter activity / symporter activity / bicarbonate transport / sodium ion transport / plasma membrane => GO:0005886 / transport across blood-brain barrier / transmembrane transporter activity / sodium ion transmembrane transport / positive regulation of glycolytic process / regulation of membrane potential / regulation of intracellular pH / transmembrane transport / basolateral plasma membrane / cell surface / extracellular exosome / identical protein binding / membrane / plasma membrane Similarity search - Function | ||||||||||||||||||||||||||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||||||||||||||||||||||||||||||||
Authors | Huynh, K.W. / Jiang, J. / Abuladze, N. / Tsirulnikov, K. / Kao, L. / Shao, X. / Newman, D. / Azimov, R. / Pushkin, A. / Zhou, Z.H. / Kurtz, I. | ||||||||||||||||||||||||||||||||||||
Funding support | United States, 11items
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Citation | Journal: Nat Commun / Year: 2018 Title: CryoEM structure of the human SLC4A4 sodium-coupled acid-base transporter NBCe1. Authors: Kevin W Huynh / Jiansen Jiang / Natalia Abuladze / Kirill Tsirulnikov / Liyo Kao / Xuesi Shao / Debra Newman / Rustam Azimov / Alexander Pushkin / Z Hong Zhou / Ira Kurtz / Abstract: Na-coupled acid-base transporters play essential roles in human biology. Their dysfunction has been linked to cancer, heart, and brain disease. High-resolution structures of mammalian Na-coupled acid- ...Na-coupled acid-base transporters play essential roles in human biology. Their dysfunction has been linked to cancer, heart, and brain disease. High-resolution structures of mammalian Na-coupled acid-base transporters are not available. The sodium-bicarbonate cotransporter NBCe1 functions in multiple organs and its mutations cause blindness, abnormal growth and blood chemistry, migraines, and impaired cognitive function. Here, we have determined the structure of the membrane domain dimer of human NBCe1 at 3.9 Å resolution by cryo electron microscopy. Our atomic model and functional mutagenesis revealed the ion accessibility pathway and the ion coordination site, the latter containing residues involved in human disease-causing mutations. We identified a small number of residues within the ion coordination site whose modification transformed NBCe1 into an anion exchanger. Our data suggest that symporters and exchangers utilize comparable transport machinery and that subtle differences in their substrate-binding regions have very significant effects on their transport mode. | ||||||||||||||||||||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6caa.cif.gz | 194 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6caa.ent.gz | 141.7 KB | Display | PDB format |
PDBx/mmJSON format | 6caa.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6caa_validation.pdf.gz | 903.8 KB | Display | wwPDB validaton report |
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Full document | 6caa_full_validation.pdf.gz | 914.8 KB | Display | |
Data in XML | 6caa_validation.xml.gz | 34.7 KB | Display | |
Data in CIF | 6caa_validation.cif.gz | 51.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ca/6caa ftp://data.pdbj.org/pub/pdb/validation_reports/ca/6caa | HTTPS FTP |
-Related structure data
Related structure data | 7441MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 116172.312 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SLC4A4, NBC, NBC1, NBCE1 / Organ: Kidney / Variant: A / Plasmid: pTT / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q9Y6R1 |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: NBCe1 Dimer / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT | |||||||||||||||
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Molecular weight | Value: 0.260 MDa / Experimental value: YES | |||||||||||||||
Source (natural) | Organism: Homo sapiens (human) / Organ: Kidney | |||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) / Cell: HEK293 / Plasmid: pTT | |||||||||||||||
Buffer solution | pH: 7.5 | |||||||||||||||
Buffer component |
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Specimen | Conc.: 0.4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Sample was purified in DDM and exchanged into Amphipols (PMAL-C8) | |||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Calibrated magnification: 36764 X / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 24 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 2 / Num. of real images: 3378 |
EM imaging optics | Energyfilter name: GIF Quantum LS / Energyfilter upper: 20 eV / Energyfilter lower: 0 eV |
Image scans | Movie frames/image: 36 / Used frames/image: 2-36 |
-Processing
Software | Name: PHENIX / Version: 1.11.1_2575: / Classification: refinement | ||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Details: CTF correction was performed during the 3D refinement in RELION Type: NONE | ||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1729419 | ||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 184561 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL | ||||||||||||||||||||||||||||||||
Refine LS restraints |
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