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Open data
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Basic information
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Title | The cryo-EM structure of hAE2 with bicarbonate | |||||||||
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![]() | chloride and bicarbonate transporter human-AE2 / TRANSPORT PROTEIN | |||||||||
Function / homology | ![]() negative regulation of CD8-positive, alpha-beta T cell differentiation / negative regulation of CD8-positive, alpha-beta T cell proliferation / positive regulation of enamel mineralization / Bicarbonate transporters / amelogenesis / monoatomic anion transmembrane transporter activity / chloride:bicarbonate antiporter activity / solute:inorganic anion antiporter activity / digestive tract development / bicarbonate transport ...negative regulation of CD8-positive, alpha-beta T cell differentiation / negative regulation of CD8-positive, alpha-beta T cell proliferation / positive regulation of enamel mineralization / Bicarbonate transporters / amelogenesis / monoatomic anion transmembrane transporter activity / chloride:bicarbonate antiporter activity / solute:inorganic anion antiporter activity / digestive tract development / bicarbonate transport / monoatomic anion transport / regulation of bone resorption / transmembrane transporter activity / osteoclast differentiation / regulation of intracellular pH / regulation of actin cytoskeleton organization / transmembrane transport / spermatogenesis / basolateral plasma membrane / apical plasma membrane / focal adhesion / enzyme binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.89 Å | |||||||||
![]() | Zhang Q / Jian L / Yao D / Rao B / Hu K / Xia Y / Cao Y | |||||||||
Funding support | ![]()
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![]() | ![]() Title: The structural basis of the pH-homeostasis mediated by the Cl/HCO exchanger, AE2. Authors: Qing Zhang / Liyan Jian / Deqiang Yao / Bing Rao / Ying Xia / Kexin Hu / Shaobai Li / Yafeng Shen / Mi Cao / An Qin / Jie Zhao / Yu Cao / ![]() Abstract: The cell maintains its intracellular pH in a narrow physiological range and disrupting the pH-homeostasis could cause dysfunctional metabolic states. Anion exchanger 2 (AE2) works at high cellular pH ...The cell maintains its intracellular pH in a narrow physiological range and disrupting the pH-homeostasis could cause dysfunctional metabolic states. Anion exchanger 2 (AE2) works at high cellular pH to catalyze the exchange between the intracellular HCO and extracellular Cl, thereby maintaining the pH-homeostasis. Here, we determine the cryo-EM structures of human AE2 in five major operating states and one transitional hybrid state. Among those states, the AE2 shows the inward-facing, outward-facing, and intermediate conformations, as well as the substrate-binding pockets at two sides of the cell membrane. Furthermore, critical structural features were identified showing an interlock mechanism for interactions among the cytoplasmic N-terminal domain and the transmembrane domain and the self-inhibitory effect of the C-terminal loop. The structural and cell-based functional assay collectively demonstrate the dynamic process of the anion exchange across membranes and provide the structural basis for the pH-sensitive pH-rebalancing activity of AE2. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15 KB 15 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 8.4 KB | Display | ![]() |
Images | ![]() | 76.1 KB | ||
Filedesc metadata | ![]() | 6 KB | ||
Others | ![]() ![]() | 59.2 MB 59.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8gvcMC ![]() 8gv8C ![]() 8gv9C ![]() 8gvaC ![]() 8gveC ![]() 8gvfC ![]() 8gvhC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Map
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Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_34290_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #1
File | emd_34290_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : hAE2 with bicarbonate
Entire | Name: hAE2 with bicarbonate |
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Components |
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-Supramolecule #1: hAE2 with bicarbonate
Supramolecule | Name: hAE2 with bicarbonate / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 137 KDa |
-Macromolecule #1: Anion exchange protein 2
Macromolecule | Name: Anion exchange protein 2 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 137.176906 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MSSAPRRPAK GADSFCTPEP ESLGPGTPGF PEQEEDELHR TLGVERFEEI LQEAGSRGGE EPGRSYGEED FEYHRQSSHH IHHPLSTHL PPDARRRKTP QGPGRKPRRR PGASPTGETP TIEEGEEDED EASEAEGARA LTQPSPVSTP SSVQFFLQED D SADRKAER ...String: MSSAPRRPAK GADSFCTPEP ESLGPGTPGF PEQEEDELHR TLGVERFEEI LQEAGSRGGE EPGRSYGEED FEYHRQSSHH IHHPLSTHL PPDARRRKTP QGPGRKPRRR PGASPTGETP TIEEGEEDED EASEAEGARA LTQPSPVSTP SSVQFFLQED D SADRKAER TSPSSPAPLP HQEATPRASK GAQAGTQVEE AEAEAVAVAS GTAGGDDGGA SGRPLPKAQP GHRSYNLQER RR IGSMTGA EQALLPRVPT DEIEAQTLAT ADLDLMKSHR FEDVPGVRRH LVRKNAKGST QSGREGREPG PTPRARPRAP HKP HEVFVE LNELLLDKNQ EPQWRETARW IKFEEDVEEE TERWGKPHVA SLSFRSLLEL RRTLAHGAVL LDLDQQTLPG VAHQ VVEQM VISDQIKAED RANVLRALLL KHSHPSDEKD FSFPRNISAG SLGSLLGHHH GQGAESDPHV TEPLMGGVPE TRLEV ERER ELPPPAPPAG ITRSKSKHEL KLLEKIPENA EATVVLVGCV EFLSRPTMAF VRLREAVELD AVLEVPVPVR FLFLLL GPS SANMDYHEIG RSISTLMSDK QFHEAAYLAD EREDLLTAIN AFLDCSVVLP PSEVQGEELL RSVAHFQRQM LKKREEQ GR LLPTGAGLEP KSAQDKALLQ MVEAAGAAED DPLRRTGRPF GGLIRDVRRR YPHYLSDFRD ALDPQCLAAV IFIYFAAL S PAITFGGLLG EKTQDLIGVS ELIMSTALQG VVFCLLGAQP LLVIGFSGPL LVFEEAFFSF CSSNHLEYLV GRVWIGFWL VFLALLMVAL EGSFLVRFVS RFTQEIFAFL ISLIFIYETF YKLVKIFQEH PLHGCSASNS SEVDGGENMT WAGARPTLGP GNRSLAGQS GQGKPRGQPN TALLSLVLMA GTFFIAFFLR KFKNSRFFPG RIRRVIGDFG VPIAILIMVL VDYSIEDTYT Q KLSVPSGF SVTAPEKRGW VINPLGEKSP FPVWMMVASL LPAILVFILI FMETQITTLI ISKKERMLQK GSGFHLDLLL IV AMGGICA LFGLPWLAAA TVRSVTHANA LTVMSKAVAP GDKPKIQEVK EQRVTGLLVA LLVGLSIVIG DLLRQIPLAV LFG IFLYMG VTSLNGIQFY ERLHLLLMPP KHHPDVTYVK KVRTLRMHLF TALQLLCLAL LWAVMSTAAS LAFPFILILT VPLR MVVLT RIFTDREMKC LDANEAEPVF DEREGVDEYN EMPMPV UniProtKB: Anion exchange protein 2 |
-Macromolecule #2: BICARBONATE ION
Macromolecule | Name: BICARBONATE ION / type: ligand / ID: 2 / Number of copies: 2 / Formula: BCT |
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Molecular weight | Theoretical: 61.017 Da |
Chemical component information | ![]() ChemComp-BCT: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 26.0 µm / Nominal defocus min: 10.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |