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- EMDB-7441: CryoEM structure of human SLC4A4 sodium-coupled acid-base transpo... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-7441 | ||||||||||||||||||||||||||||||||||||
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Title | CryoEM structure of human SLC4A4 sodium-coupled acid-base transporter NBCe1 | ||||||||||||||||||||||||||||||||||||
![]() | Electrogenic Sodium Bicarbonate Cotransporter, SLC4A4, NBCe1 | ||||||||||||||||||||||||||||||||||||
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![]() | SLC4A4 / Electrogenic Sodium-Coupled Bicarbonate Cotransporters / TRANSPORT PROTEIN / NBCe1 | ||||||||||||||||||||||||||||||||||||
Function / homology | ![]() 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 / transmembrane transporter activity / transport across blood-brain barrier / 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 | ![]() | ||||||||||||||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||||||||||||||||||||||||||||||||
![]() | Huynh KW / Jiang J | ||||||||||||||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 25.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.2 KB 16.2 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 6.7 KB | Display | ![]() |
Images | ![]() | 25.1 KB | ||
Filedesc metadata | ![]() | 6.6 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 561.3 KB | Display | ![]() |
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Full document | ![]() | 560.9 KB | Display | |
Data in XML | ![]() | 9.2 KB | Display | |
Data in CIF | ![]() | 12 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6caaMC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Electrogenic Sodium Bicarbonate Cotransporter, SLC4A4, NBCe1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.36 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : NBCe1 Dimer
Entire | Name: NBCe1 Dimer |
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Components |
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-Supramolecule #1: NBCe1 Dimer
Supramolecule | Name: NBCe1 Dimer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 260 KDa |
-Macromolecule #1: Electrogenic sodium bicarbonate cotransporter 1
Macromolecule | Name: Electrogenic sodium bicarbonate cotransporter 1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 116.172312 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MSTENVEGKP SNLGERGRAR SSTFLRVVQP MFNHSIFTSA VSPAAERIRF ILGEEDDSPA PPQLFTELDE LLAVDGQEME WKETARWIK FEEKVEQGGE RWSKPHVATL SLHSLFELRT CMEKGSIMLD REASSLPQLV EMIVDHQIET GLLKPELKDK V TYTLLRKH ...String: MSTENVEGKP SNLGERGRAR SSTFLRVVQP MFNHSIFTSA VSPAAERIRF ILGEEDDSPA PPQLFTELDE LLAVDGQEME WKETARWIK FEEKVEQGGE RWSKPHVATL SLHSLFELRT CMEKGSIMLD REASSLPQLV EMIVDHQIET GLLKPELKDK V TYTLLRKH RHQTKKSNLR SLADIGKTVS SASRMFTNPD NGSPAMTHRN LTSSSLNDIS DKPEKDQLKN KFMKKLPRDA EA SNVLVGE VDFLDTPFIA FVRLQQAVML GALTEVPVPT RFLFILLGPK GKAKSYHEIG RAIATLMSDE VFHDIAYKAK DRH DLIAGI DEFLDEVIVL PPGEWDPAIR IEPPKSLPSS DKRKNMYSGG ENVQMNGDTP HDGGHGGGGH GDCEELQRTG RFCG GLIKD IKRKAPFFAS DFYDALNIQA LSAILFIYLA TVTNAITFGG LLGDATDNMQ GVLESFLGTA VSGAIFCLFA GQPLT ILSS TGPVLVFERL LFNFSKDNNF DYLEFRLWIG LWSAFLCLIL VATDASFLVQ YFTRFTEEGF SSLISFIFIY DAFKKM IKL ADYYPINSNF KVGYNTLFSC TCVPPDPANI SISNDTTLAP EYLPTMSSTD MYHNTTFDWA FLSKKECSKY GGNLVGN NC NFVPDITLMS FILFLGTYTS SMALKKFKTS PYFPTTARKL ISDFAIILSI LIFCVIDALV GVDTPKLIVP SEFKPTSP N RGWFVPPFGE NPWWVCLAAA IPALLVTILI FMDQQITAVI VNRKEHKLKK GAGYHLDLFW VAILMVICSL MALPWYVAA TVISIAHIDS LKMETETSAP GEQPKFLGVR EQRVTGTLVF ILTGLSVFMA PILKFIPMPV LYGVFLYMGV ASLNGVQFMD RLKLLLMPL KHQPDFIYLR HVPLRRVHLF TFLQVLCLAL LWILKSTVAA IIFPVMILAL VAVRKGMDYL FSQHDLSFLD D VIPEKDKK KKEDEKKKKK KKGSLDSDND DSDCPYSEKV PSIKIPMDIM EQQPFLSDSK PSDRERSPTF LERHTSC UniProtKB: Electrogenic sodium bicarbonate cotransporter 1 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.40 mg/mL | |||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE | |||||||||
Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV | |||||||||
Details | Sample was purified in DDM and exchanged into Amphipols (PMAL-C8) |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Quantum LS / Energy filter - Lower energy threshold: 0 eV / Energy filter - Upper energy threshold: 20 eV |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Frames/image: 2-36 / Number grids imaged: 2 / Number real images: 3378 / Average electron dose: 24.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Calibrated magnification: 36764 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL |
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Output model | ![]() PDB-6caa: |