7dxe: Difference between revisions

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<StructureSection load='7dxe' size='340' side='right'caption='[[7dxe]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
<StructureSection load='7dxe' size='340' side='right'caption='[[7dxe]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7dxe]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DXE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DXE FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DXE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DXE FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=98R:[(2S)-2-[(E)-octadec-10-enoyl]oxy-3-oxidanyl-propyl]+octadec-10-enoate'>98R</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene>, <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]] 3.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=98R:[(2S)-2-[(E)-octadec-10-enoyl]oxy-3-oxidanyl-propyl]+octadec-10-enoate'>98R</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=7dxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dxe OCA], [https://pdbe.org/7dxe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dxe RCSB], [https://www.ebi.ac.uk/pdbsum/7dxe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dxe ProSAT]</span></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=7dxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dxe OCA], [https://pdbe.org/7dxe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dxe RCSB], [https://www.ebi.ac.uk/pdbsum/7dxe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dxe ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[https://www.uniprot.org/uniprot/TRPC3_HUMAN TRPC3_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[[https://www.uniprot.org/uniprot/TRPC3_HUMAN TRPC3_HUMAN]] Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Activated by diacylglycerol (DAG) in a membrane-delimited fashion, independently of protein kinase C, and by inositol 1,4,5-triphosphate receptors (ITPR) with bound IP3. May also be activated by internal calcium store depletion.<ref>PMID:20095964</ref> <ref>PMID:8646775</ref> <ref>PMID:9417057</ref> <ref>PMID:9930701</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
TRPC3 and TRPC6 channels are calcium-permeable non-selective cation channels that are involved in many physiological processes. The gain-of-function (GOF) mutations of TRPC6 lead to familial focal segmental glomerulosclerosis (FSGS) in humans, but their pathogenic mechanism remains elusive. Here, we report the cryo-EM structures of human TRPC3 in both high-calcium and low-calcium conditions. Based on these structures and accompanying electrophysiological studies, we identified both inhibitory and activating calcium-binding sites in TRPC3 that couple intracellular calcium concentrations to the basal channel activity. These calcium sensors are also structurally and functionally conserved in TRPC6. We uncovered that the GOF mutations of TRPC6 activate the channel by allosterically abolishing the inhibitory effects of intracellular calcium. Furthermore, structures of human TRPC6 in complex with two chemically distinct inhibitors bound at different ligand-binding pockets reveal different conformations of the transmembrane domain, providing templates for further structure-based drug design targeting TRPC6-related diseases such as FSGS.
Structural mechanism of human TRPC3 and TRPC6 channel regulation by their intracellular calcium-binding sites.,Guo W, Tang Q, Wei M, Kang Y, Wu JX, Chen L Neuron. 2022 Mar 16;110(6):1023-1035.e5. doi: 10.1016/j.neuron.2021.12.023. Epub , 2022 Jan 19. PMID:35051376<ref>PMID:35051376</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7dxe" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Chen, L]]
[[Category: Chen L]]
[[Category: Guo, W]]
[[Category: Guo W]]
[[Category: Calcium]]
[[Category: Channel]]
[[Category: Gain of function]]
[[Category: Membrane protein]]
[[Category: Trpc]]
[[Category: Trpc3]]

Latest revision as of 05:42, 5 June 2024

Structure of TRPC3 gain of function mutation R803C at 3.2 angstrom in 1340nM free calcium state

7dxe, resolution 3.20Å

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