View source for 8tkd


==Human Type 3 IP3 Receptor - Preactivated State (+IP3/ATP)==
<StructureSection load='8tkd' size='340' side='right'caption='[[8tkd]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8tkd]] 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=8TKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8TKD 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]] 3.7&#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=8tkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8tkd OCA], [https://pdbe.org/8tkd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8tkd RCSB], [https://www.ebi.ac.uk/pdbsum/8tkd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8tkd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ITPR3_HUMAN ITPR3_HUMAN] Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Inositol 1,4,5-trisphosphate receptors (IP(3)Rs) are endoplasmic reticulum Ca(2+) channels whose biphasic dependence on cytosolic Ca(2+) gives rise to Ca(2+) oscillations that regulate fertilization, cell division and cell death. Despite the critical roles of IP(3)R-mediated Ca(2+) responses, the structural underpinnings of the biphasic Ca(2+) dependence that underlies Ca(2+) oscillations are incompletely understood. Here, we collect cryo-EM images of an IP(3)R with Ca(2+) concentrations spanning five orders of magnitude. Unbiased image analysis reveals that Ca(2+) binding does not explicitly induce conformational changes but rather biases a complex conformational landscape consisting of resting, preactivated, activated, and inhibited states. Using particle counts as a proxy for relative conformational free energy, we demonstrate that Ca(2+) binding at a high-affinity site allows IP(3)Rs to activate by escaping a low-energy resting state through an ensemble of preactivated states. At high Ca(2+) concentrations, IP(3)Rs preferentially enter an inhibited state stabilized by a second, low-affinity Ca(2+) binding site. Together, these studies provide a mechanistic basis for the biphasic Ca(2+)-dependence of IP(3)R channel activity.

Structural titration reveals Ca(2+)-dependent conformational landscape of the IP(3) receptor.,Paknejad N, Sapuru V, Hite RK Nat Commun. 2023 Oct 28;14(1):6897. doi: 10.1038/s41467-023-42707-3. PMID:37898605<ref>PMID:37898605</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8tkd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hite RK]]
[[Category: Paknejad N]]
[[Category: Sapuru V]]