View source for 8jni


==Structure of AE2 in complex with PIP2==
<StructureSection load='8jni' size='340' side='right'caption='[[8jni]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8jni]] 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=8JNI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JNI 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]] 3.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PT5:(1S)-2-{[(R)-HYDROXY{[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIHYDROXY-4,5-BIS(PHOSPHONOOXY)CYCLOHEXYL]OXY}PHOSPHORYL]OXY}-1-[(OCTADECANOYLOXY)METHYL]ETHYL+(8E,11E)-ICOSA-5,8,11,14-TETRAENOATE'>PT5</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=8jni FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jni OCA], [https://pdbe.org/8jni PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jni RCSB], [https://www.ebi.ac.uk/pdbsum/8jni PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jni 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 ==
Anion exchanger 2 (AE2) is an electroneutral Na(+)-independent Cl(-)/HCO(3)(-) exchanger belongs to the SLC4 transporter family. The widely expressed AE2 participates in a variety of physiological processes, including transepithelial acid-base secretion and osteoclastogenesis. Both the transmembrane domains (TMDs) and the N-terminal cytoplasmic domain (NTD) are involved in regulation of AE2 activity. However, the regulatory mechanism remains unclear. Here, we report a 3.2 A cryo-EM structure of the AE2 TMDs in complex with PIP(2) and a 3.3 A full-length mutant AE2 structure in the resting state without PIP(2). We demonstrate that PIP(2) at the TMD dimer interface is involved in the substrate exchange process. Mutation in the PIP(2) binding site leads to the displacement of TM7 and further stabilizes the interaction between the TMD and the NTD. Reduced substrate transport activity and conformation similar to AE2 in acidic pH indicating the central contribution of PIP(2) to the function of AE2.

Structural and functional insights into the lipid regulation of human anion exchanger 2.,Zhang W, Ding D, Lu Y, Chen H, Jiang P, Zuo P, Wang G, Luo J, Yin Y, Luo J, Yin Y Nat Commun. 2024 Jan 26;15(1):759. doi: 10.1038/s41467-024-44966-0. PMID:38272905<ref>PMID:38272905</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8jni" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ding D]]
[[Category: Yin YX]]