View source for 8gv8


==The cryo-EM structure of hAE2 with DIDS==
<StructureSection load='8gv8' size='340' side='right'caption='[[8gv8]], [[Resolution|resolution]] 3.08&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8gv8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GV8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GV8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.08&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4KU:2,2-ETHANE-1,2-DIYLBIS{5-[(SULFANYLMETHYL)AMINO]BENZENESULFONIC+ACID}'>4KU</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8gv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gv8 OCA], [https://pdbe.org/8gv8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gv8 RCSB], [https://www.ebi.ac.uk/pdbsum/8gv8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gv8 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/B3A2_HUMAN B3A2_HUMAN] The disease may be caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/B3A2_HUMAN B3A2_HUMAN] Sodium-independent anion exchanger which mediates the electroneutral exchange of chloride for bicarbonate ions across the cell membrane (PubMed:15184086, PubMed:34668226). Plays an important role in osteoclast differentiation and function (PubMed:34668226). Regulates bone resorption and calpain-dependent actin cytoskeleton organization in osteoclasts via anion exchange-dependent control of pH (By similarity). Essential for intracellular pH regulation in CD8(+) T-cells upon CD3 stimulation, modulating CD8(+) T-cell responses (By similarity).[UniProtKB:P13808]<ref>PMID:15184086</ref> <ref>PMID:34668226</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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(3)(-) 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.

The structural basis of the pH-homeostasis mediated by the Cl(-)/HCO(3)(-) exchanger, AE2.,Zhang Q, Jian L, Yao D, Rao B, Xia Y, Hu K, Li S, Shen Y, Cao M, Qin A, Zhao J, Cao Y Nat Commun. 2023 Mar 31;14(1):1812. doi: 10.1038/s41467-023-37557-y. PMID:37002221<ref>PMID:37002221</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8gv8" style="background-color:#fffaf0;"></div>

==See Also==
*[[Anion exchange protein 3D structures|Anion exchange protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cao Y]]
[[Category: Hu K]]
[[Category: Jian L]]
[[Category: Rao B]]
[[Category: Xia Y]]
[[Category: Yao D]]
[[Category: Zhang Q]]