View source for 9lzy


==Cryo-EM structure of homomeric TRPC channel with agonists, class 1==
<StructureSection load='9lzy' size='340' side='right'caption='[[9lzy]], [[Resolution|resolution]] 2.43&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9lzy]] 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=9LZY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9LZY 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]] 2.43&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=657:6-(trifluoromethoxy)-1,3-benzothiazol-2-amine'>657</scene>, <scene name='pdbligand=A1L55:[(1~{S},2~{R},5~{R},6~{R},7~{S},8~{R},10~{R})-1,5-dimethyl-10-(2-oxidanylethanoyloxy)-8-propan-2-yl-11-oxatricyclo[6.2.1.0^{2,6}]undecan-7-yl]+(~{E})-3-phenylprop-2-enoate'>A1L55</scene>, <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=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=9lzy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9lzy OCA], [https://pdbe.org/9lzy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9lzy RCSB], [https://www.ebi.ac.uk/pdbsum/9lzy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9lzy 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Transient receptor potential (TRP) ion channels form heteromers through combinatorial associations of distinct subunits, contributing to the diversity of TRP channel functions. Among them, TRPC5, which forms a heteromer with TRPC1, represents an attractive pharmaceutical target for treating anxiety and depression. Here, we present the cryo-electron microscopy structure of the human TRPC1/C5 heteromer, composed of one TRPC1 subunit and three TRPC5 subunits. The incorporation of TRPC1 into the heteromer disrupts the C(4) symmetry of the TRPC5 homotetramer, resulting in a distinct ion conduction pathway characterized by an asymmetrically constricted selectivity filter and an asymmetric lower gate. The TRPC1/C5 heteromer displays recognizable structural features compared to the TRPC1/C4 heteromer, including a noncanonically tilted coiled-coil domain and a distinct intersubunit interactions. Furthermore, we elucidate the structures of human TRPC5 bound to the TRPC1/4/5-specific agonist, (-)-Englerin A. Our findings establish a foundation for exploring the diversity of heteromeric TRP channels and pave the way for targeting TRPC1/C5 as a therapeutic strategy.

Molecular architecture of the human TRPC1/C5 heteromeric channel.,Kim SH, Park H, Kim J, Kang H, Won J, Lee BC, So I, Lee HH Nat Commun. 2025 Dec 10;17(1):317. doi: 10.1038/s41467-025-67024-9. PMID:41372144<ref>PMID:41372144</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9lzy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kim S-H]]
[[Category: Lee HH]]
[[Category: Park H]]