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| | <SX load='6uqk' size='340' side='right' viewer='molstar' caption='[[6uqk]], [[Resolution|resolution]] 3.77Å' scene=''> | | <SX load='6uqk' size='340' side='right' viewer='molstar' caption='[[6uqk]], [[Resolution|resolution]] 3.77Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6uqk]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UQK OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UQK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6uqk]] 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=6UQK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UQK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.77Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">itpr3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6uqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uqk OCA], [https://pdbe.org/6uqk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uqk RCSB], [https://www.ebi.ac.uk/pdbsum/6uqk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uqk ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6uqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uqk OCA], [http://pdbe.org/6uqk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uqk RCSB], [http://www.ebi.ac.uk/pdbsum/6uqk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uqk ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [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. |
| - | Calcium-mediated signaling through inositol 1,4,5-triphosphate receptors (IP3Rs) is essential for the regulation of numerous physiological processes, including fertilization, muscle contraction, apoptosis, secretion, and synaptic plasticity. Deregulation of IP3Rs leads to pathological calcium signaling and is implicated in many common diseases, including cancer and neurodegenerative, autoimmune, and metabolic diseases. Revealing the mechanism of activation and inhibition of this ion channel will be critical to an improved understanding of the biological processes that are controlled by IP3Rs. Here, we report structural findings of the human type-3 IP3R (IP3R-3) obtained by cryo-EM (at an overall resolution of 3.8 A), revealing an unanticipated regulatory mechanism where a loop distantly located in the primary sequence occupies the IP3-binding site and competitively inhibits IP3 binding. We propose that this inhibitory mechanism must differ qualitatively among IP3R subtypes because of their diverse loop sequences, potentially serving as a key molecular determinant of subtype-specific calcium signaling in IP3Rs. In summary, our structural characterization of human IP3R-3 provides critical insights into the mechanistic function of IP3Rs and into subtype-specific regulation of these important calcium-regulatory channels.
| + | |
| | | | |
| - | Cryo-EM structure of human type-3 inositol triphosphate receptor reveals the presence of a self-binding peptide that acts as an antagonist.,Azumaya CM, Linton EA, Risener CJ, Nakagawa T, Karakas E J Biol Chem. 2020 Jan 8. pii: RA119.011570. doi: 10.1074/jbc.RA119.011570. PMID:31915246<ref>PMID:31915246</ref>
| + | ==See Also== |
| - | | + | *[[Inositol 1%2C4%2C5-Trisphosphate Receptor|Inositol 1%2C4%2C5-Trisphosphate Receptor]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6uqk" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Azumaya, C M]] | + | [[Category: Azumaya CM]] |
| - | [[Category: Karakas, E]] | + | [[Category: Karakas E]] |
| - | [[Category: Linton, E A]] | + | [[Category: Linton EA]] |
| - | [[Category: Nakagawa, T]] | + | [[Category: Nakagawa T]] |
| - | [[Category: Risener, C J]] | + | [[Category: Risener CJ]] |
| - | [[Category: Calcium channel]]
| + | |
| - | [[Category: Cryoelectron microscopy]]
| + | |
| - | [[Category: Inositol trisphosphate receptor]]
| + | |
| - | [[Category: Insp3r]]
| + | |
| - | [[Category: Ion channel]]
| + | |
| - | [[Category: Ip3r]]
| + | |
| - | [[Category: Isothermal titration calorimetry]]
| + | |
| - | [[Category: Self binding peptide]]
| + | |
| - | [[Category: Transport protein]]
| + | |
