View source for 9iws


==Cryo EM structure of human phosphate channel XPR1 in complex with IP7==
<StructureSection load='9iws' size='340' side='right'caption='[[9iws]], [[Resolution|resolution]] 2.86&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9iws]] 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=9IWS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9IWS 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]] 2.86&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I7P:(1R,2R,3S,4S,5R,6S)-2,3,4,5,6-PENTAKIS(PHOSPHONOOXY)CYCLOHEXYL+TRIHYDROGEN+DIPHOSPHATE'>I7P</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=9iws FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9iws OCA], [https://pdbe.org/9iws PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9iws RCSB], [https://www.ebi.ac.uk/pdbsum/9iws PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9iws ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/S53A1_HUMAN S53A1_HUMAN] Bilateral striopallidodentate calcinosis. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/S53A1_HUMAN S53A1_HUMAN] Inorganic ion transporter that mediates phosphate ion export across plasma membrane. Plays a major role in phosphate homeostasis, preventing intracellular phosphate accumulation and possible calcium phosphate precipitation, ultimately preserving calcium signaling. The molecular mechanism of phosphate transport, whether electrogenic, electroneutral or coupled to other ions, remains to be elucidated (By similarity) (PubMed:23791524, PubMed:25938945, PubMed:31043717). Binds inositol hexakisphosphate (Ins6P) and similar inositol polyphosphates, such as 5-diphospho-inositol pentakisphosphate (5-InsP7), important intracellular signaling molecules involved in regulation of phosphate flux (PubMed:27080106).[UniProtKB:Q9Z0U0]<ref>PMID:23791524</ref> <ref>PMID:25938945</ref> <ref>PMID:27080106</ref> <ref>PMID:31043717</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Precise regulation of intracellular phosphate (Pi) is critical for cellular function, with XPR1 serving as the sole Pi exporter in humans. The mechanism of Pi efflux, activated by inositol pyrophosphates (PP-IPs), has remained unclear. This study presents cryo-electron microscopy structures of XPR1 in multiple conformations, revealing a transmembrane pathway for Pi export and a dual-binding activation pattern by PP-IPs. A canonical binding site is located at the dimeric interface of SPX domains, and a second site, biased toward PP-IPs, is found between the transmembrane and SPX domains. By integrating structural studies with electrophysiological analyses, we characterize XPR1 as an IPs/PP-IPs-activated phosphate channel. The interplay among its TMDs, SPX domains, and IPs/PP-IPs orchestrates the conformational transition between its closed and open states.

Structural basis for inositol pyrophosphate gating of the phosphate channel XPR1.,Lu Y, Yue CX, Zhang L, Yao D, Xia Y, Zhang Q, Zhang X, Li S, Shen Y, Cao M, Guo CR, Qin A, Zhao J, Zhou L, Yu Y, Cao Y Science. 2024 Sep 26:eadp3252. doi: 10.1126/science.adp3252. PMID:39325866<ref>PMID:39325866</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9iws" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cao Y]]
[[Category: Lu Y]]
[[Category: Yao D]]
[[Category: Yu Y]]
[[Category: Yue C]]
[[Category: Zhang L]]