View source for 9ymz


==Human type 2 IP3 receptor in the inactive-like state (IP3/ATP)==
<StructureSection load='9ymz' size='340' side='right'caption='[[9ymz]], [[Resolution|resolution]] 3.14&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9ymz]] is a 4 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=9YMZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9YMZ 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]] 3.14&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=I3P:D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE'>I3P</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=9ymz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ymz OCA], [https://pdbe.org/9ymz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ymz RCSB], [https://www.ebi.ac.uk/pdbsum/9ymz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ymz ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ITPR2_HUMAN ITPR2_HUMAN] Isolated generalized anhidrosis with normal sweat glands. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/ITPR2_HUMAN ITPR2_HUMAN] Inositol 1,4,5-trisphosphate-gated calcium channel that upon inositol 1,4,5-trisphosphate binding transports calcium from the endoplasmic reticulum lumen to cytoplasm. Exists in two states; a long-lived closed state where the channel is essentially 'parked' with only very rare visits to an open state and that ligands facilitate the transition from the 'parked' state into a 'drive' mode represented by periods of bursting activity (By similarity).[UniProtKB:Q9Z329]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)Rs) are tetrameric ER Ca(2+) channels that shape intracellular Ca(2+) signaling in response to IP(3), regulating diverse physiological processes. The structural basis for subtype-specific regulation among the three subtypes (IP(3)R-1-3) remains incompletely understood due to the lack of IP(3)R-2 structures. Here, we report cryo-electron microscopy (cryo-EM) structures of human IP(3)R-2 in distinct conformations in the presence and absence of IP(3), Ca(2+), and ATP. These structures define the conformational landscape of IP(3)R-2, delineate ligand-binding interactions, and reveal shared architectural features alongside isoform-specific differences. We also resolve ligand-dependent IP(3)R-2 assemblies, identifying a conformation-dependent inter-channel interface. Live-cell imaging demonstrates that IP(3)R-2 undergoes clustering following ligand-induced Ca(2+) release, and disruption of this interface selectively abolishes clustering without impairing channel activity. Together, these findings provide a structural framework for human IP(3)R-2 and establish a mechanism linking ligand-dependent conformational changes to inter-channel interactions and post-activation cellular clustering.

Conformational landscape and ligand-dependent clustering of the human type 2 IP(3) receptor.,Liu C, Lan YJ, Kushner MG, Tang Q, Karakas E Nat Commun. 2026 Jun 19. doi: 10.1038/s41467-026-74494-y. PMID:42315508<ref>PMID:42315508</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9ymz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Karakas E]]
[[Category: Lan Y]]
[[Category: Liu C]]
[[Category: Tang Q]]