+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-34293 | |||||||||
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Title | Human AE2 in acidic KNO3 | |||||||||
Map data | AE2-acidic-KNO3, C2 symmetry | |||||||||
Sample |
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Function / homology | Function and homology information 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 / bicarbonate transport / digestive tract development ...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 / bicarbonate transport / digestive tract development / monoatomic anion transport / regulation of bone resorption / transmembrane transporter activity / osteoclast differentiation / regulation of actin cytoskeleton organization / regulation of intracellular pH / transmembrane transport / spermatogenesis / basolateral plasma membrane / apical plasma membrane / focal adhesion / enzyme binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.32 Å | |||||||||
Authors | Zhang Q / Jian L / Yao D / Rao B / Hu K / Xia Y / Cao Y | |||||||||
Funding support | China, 2 items
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Citation | Journal: Nat Commun / Year: 2023 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 | emd_34293.map.gz | 59.6 MB | EMDB map data format | |
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Header (meta data) | emd-34293-v30.xml emd-34293.xml | 15.4 KB 15.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_34293_fsc.xml | 8.4 KB | Display | FSC data file |
Images | emd_34293.png | 144 KB | ||
Others | emd_34293_half_map_1.map.gz emd_34293_half_map_2.map.gz | 59.1 MB 59.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-34293 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-34293 | HTTPS FTP |
-Related structure data
Related structure data | 8gvhMC 8gv8C 8gv9C 8gvaC 8gvcC 8gveC 8gvfC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_34293.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | AE2-acidic-KNO3, C2 symmetry | ||||||||||||||||||||
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: AE2-acidic-KNO3 half map B
File | emd_34293_half_map_1.map | ||||||||||||
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Annotation | AE2-acidic-KNO3 half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: AE2-acidic-KNO3 half map A
File | emd_34293_half_map_2.map | ||||||||||||
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Annotation | AE2-acidic-KNO3 half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Anion exchange protein 2 in acidic pH
Entire | Name: Anion exchange protein 2 in acidic pHIon exchange |
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Components |
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-Supramolecule #1: Anion exchange protein 2 in acidic pH
Supramolecule | Name: Anion exchange protein 2 in acidic pH / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
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: Homo sapiens (human) |
Molecular weight | Theoretical: 137.176906 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
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 |
-Macromolecule #2: CHOLESTEROL HEMISUCCINATE
Macromolecule | Name: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 2 / Number of copies: 2 / Formula: Y01 |
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Molecular weight | Theoretical: 486.726 Da |
Chemical component information | ChemComp-Y01: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.6 µm / Nominal defocus min: 1.0 µm |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |