+Open data
-Basic information
Entry | Database: PDB / ID: 8y85 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Human AE3 with NaHCO3- and DIDS | |||||||||
Components | Anion exchange protein 3 | |||||||||
Keywords | TRANSPORT PROTEIN/INHIBITOR / TRANSPORT PROTEIN-INHIBITOR complex | |||||||||
Function / homology | Function and homology information pH reduction / cardiac muscle cell action potential / Bicarbonate transporters / cardiac conduction / chloride:bicarbonate antiporter activity / solute:inorganic anion antiporter activity / bicarbonate transport / bicarbonate transmembrane transporter activity / regulation of cardiac muscle cell action potential / transmembrane transporter activity ...pH reduction / cardiac muscle cell action potential / Bicarbonate transporters / cardiac conduction / chloride:bicarbonate antiporter activity / solute:inorganic anion antiporter activity / bicarbonate transport / bicarbonate transmembrane transporter activity / regulation of cardiac muscle cell action potential / transmembrane transporter activity / transport across blood-brain barrier / regulation of intracellular pH / transmembrane transport / external side of plasma membrane / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.73 Å | |||||||||
Authors | Jian, L. / Zhang, Q. / Yao, D. / Wang, Q. / Xia, Y. / Qin, A. / Cao, Y. | |||||||||
Funding support | China, 2items
| |||||||||
Citation | Journal: Nat Commun / Year: 2024 Title: The structural insight into the functional modulation of human anion exchanger 3. Authors: Liyan Jian / Qing Zhang / Deqiang Yao / Qian Wang / Moxin Chen / Ying Xia / Shaobai Li / Yafeng Shen / Mi Cao / An Qin / Lin Li / Yu Cao / Abstract: Anion exchanger 3 (AE3) is pivotal in regulating intracellular pH across excitable tissues, yet its structural intricacies and functional dynamics remain underexplored compared to other anion ...Anion exchanger 3 (AE3) is pivotal in regulating intracellular pH across excitable tissues, yet its structural intricacies and functional dynamics remain underexplored compared to other anion exchangers. This study unveils the structural insights into human AE3, including the cryo-electron microscopy structures for AE3 transmembrane domains (TMD) and a chimera combining AE3 N-terminal domain (NTD) with AE2 TMD (hAE32). Our analyzes reveal a substrate binding site, an NTD-TMD interlock mechanism, and a preference for an outward-facing conformation. Unlike AE2, which has more robust acid-loading capabilities, AE3's structure, including a less stable inward-facing conformation due to missing key NTD-TMD interactions, contributes to its moderated pH-modulating activity and increased sensitivity to the inhibitor DIDS. These structural differences underline AE3's distinct functional roles in specific tissues and underscore the complex interplay between structural dynamics and functional specificity within the anion exchanger family, enhancing our understanding of the physiological and pathological roles of the anion exchanger family. | |||||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8y85.cif.gz | 233.9 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8y85.ent.gz | 171.4 KB | Display | PDB format |
PDBx/mmJSON format | 8y85.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8y85_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 8y85_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 8y85_validation.xml.gz | 42.3 KB | Display | |
Data in CIF | 8y85_validation.cif.gz | 61.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/y8/8y85 ftp://data.pdbj.org/pub/pdb/validation_reports/y8/8y85 | HTTPS FTP |
-Related structure data
Related structure data | 39034MC 8y86C 8y8kC 8zleC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 135961.516 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: AE3 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P48751 #2: Chemical | #3: Chemical | Has ligand of interest | Y | |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Anion exchange protein 3 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
---|---|
Molecular weight | Value: 0.135 MDa / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2600 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
---|---|
3D reconstruction | Resolution: 2.73 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 968201 / Symmetry type: POINT |