View source for 8gvw


==Cryo-EM structure of the human TRPC5 ion channel in lipid nanodiscs, class2==
<StructureSection load='8gvw' size='340' side='right'caption='[[8gvw]], [[Resolution|resolution]] 3.59&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8gvw]] 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=8GVW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GVW 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]] 3.59&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene>, <scene name='pdbligand=PTY:PHOSPHATIDYLETHANOLAMINE'>PTY</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene>, <scene name='pdbligand=YZY:(2S)-2-(HEXADECANOYLOXY)-3-HYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>YZY</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=8gvw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gvw OCA], [https://pdbe.org/8gvw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gvw RCSB], [https://www.ebi.ac.uk/pdbsum/8gvw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gvw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TRPC5_HUMAN TRPC5_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. Has also been shown to be calcium-selective (By similarity). May also be activated by intracellular calcium store depletion. Mediates calcium-dependent phosphatidylserine externalization and apoptosis in neurons via its association with PLSCR1 (By similarity).[UniProtKB:Q9QX29]<ref>PMID:16284075</ref> 
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== Publication Abstract from PubMed ==
G-protein coupled receptors (GPCRs) and ion channels serve as key molecular switches through which extracellular stimuli are transformed into intracellular effects, and it has long been postulated that ion channels are direct effector molecules of the alpha subunit of G-proteins (Galpha). However, no complete structural evidence supporting the direct interaction between Galpha and ion channels is available. Here, we present the cryo-electron microscopy structures of the human transient receptor potential canonical 5 (TRPC5)-Galpha(i3) complexes with a 4:4 stoichiometry in lipid nanodiscs. Remarkably, Galpha(i3) binds to the ankyrin repeat edge of TRPC5 ~ 50 A away from the cell membrane. Electrophysiological analysis shows that Galpha(i3) increases the sensitivity of TRPC5 to phosphatidylinositol 4,5-bisphosphate (PIP(2)), thereby rendering TRPC5 more easily opened in the cell membrane, where the concentration of PIP(2) is physiologically regulated. Our results demonstrate that ion channels are one of the direct effector molecules of Galpha proteins triggered by GPCR activation-providing a structural framework for unraveling the crosstalk between two major classes of transmembrane proteins: GPCRs and ion channels.

Molecular architecture of the Galpha(i)-bound TRPC5 ion channel.,Won J, Kim J, Jeong H, Kim J, Feng S, Jeong B, Kwak M, Ko J, Im W, So I, Lee HH Nat Commun. 2023 May 3;14(1):2550. doi: 10.1038/s41467-023-38281-3. PMID:37137991<ref>PMID:37137991</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 8gvw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Jeong H]]
[[Category: Lee HH]]
[[Category: Won J]]