View source for 8s90


==Cryo-EM structure of octameric human CALHM1 (I109W) in complex with ruthenium red (C1)==
<StructureSection load='8s90' size='340' side='right'caption='[[8s90]], [[Resolution|resolution]] 4.73&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8s90]] is a 8 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=8S90 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8S90 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]] 4.73&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=R2R:ruthenium(6+)+azanide+pentaamino(oxido)ruthenium+(1/4/2)'>R2R</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=8s90 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8s90 OCA], [https://pdbe.org/8s90 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8s90 RCSB], [https://www.ebi.ac.uk/pdbsum/8s90 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8s90 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CAHM1_HUMAN CAHM1_HUMAN] Pore-forming subunit of gustatory voltage-gated ion channels required for sensory perception of sweet, bitter and umami tastes (By similarity). With CALHM3 forms a fast-activating voltage-gated ATP-release channel in type II taste bud cells, ATP acting as a neurotransmitter to activate afferent neural gustatory pathways (By similarity) (PubMed:23467090). Acts both as a voltage-gated and calcium-activated ion channel: mediates neuronal excitability in response to membrane depolarization and low extracellular Ca(2+) concentration (PubMed:22711817, PubMed:23300080). Has poor ion selectivity and forms a wide pore (around 14 Angstroms) that mediates permeation of small ions including Ca(2+), Na(+), K(+) and Cl(-), as well as larger ions such as ATP(4-) (PubMed:22711817, PubMed:23300080, PubMed:32832629, PubMed:37380652). Mediates Ca(2+) influx and downstream activation of the ERK1 and ERK2 cascade in neurons (PubMed:23345406). Triggers endoplasmic reticulum stress by reducing the Ca(2+) content of the endoplasmic reticulum (PubMed:21574960). May indirectly control amyloid precursor protein (APP) proteolysis and aggregated amyloid-beta (Abeta) peptides levels in a Ca(2+)-dependent manner (PubMed:18585350).[UniProtKB:D3Z291]<ref>PMID:18585350</ref> <ref>PMID:21574960</ref> <ref>PMID:22711817</ref> <ref>PMID:23300080</ref> <ref>PMID:23345406</ref> <ref>PMID:23467090</ref> <ref>PMID:32832629</ref> <ref>PMID:37380652</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Calcium homeostasis modulator 1 (CALHM1) is a voltage-dependent channel involved in neuromodulation and gustatory signaling. Despite recent progress in the structural biology of CALHM1, insights into functional regulation, pore architecture, and channel blockade remain limited. Here we present the cryo-EM structure of human CALHM1, revealing an octameric assembly pattern similar to the non-mammalian CALHM1s and the lipid-binding pocket conserved across species. We demonstrate by MD simulations that this pocket preferentially binds a phospholipid over cholesterol to stabilize its structure and regulate the channel activities. Finally, we show that residues in the amino-terminal helix form the channel pore that ruthenium red binds and blocks.

Structure of human CALHM1 reveals key locations for channel regulation and blockade by ruthenium red.,Syrjanen JL, Epstein M, Gomez R, Furukawa H Nat Commun. 2023 Jun 28;14(1):3821. doi: 10.1038/s41467-023-39388-3. PMID:37380652<ref>PMID:37380652</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8s90" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Furukawa H]]
[[Category: Syrjanen JL]]