View source for 6uiw


==Cryo-EM structure of human CALHM2 in a ruthenium red-bound inhibited state==
<SX load='6uiw' size='340' side='right' viewer='molstar' caption='[[6uiw]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6uiw]] is a 11 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=6UIW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UIW 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]] 2.7&#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=6uiw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uiw OCA], [https://pdbe.org/6uiw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uiw RCSB], [https://www.ebi.ac.uk/pdbsum/6uiw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uiw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CAHM2_HUMAN CAHM2_HUMAN] Pore-forming subunit of a voltage-gated ion channel.[UniProtKB:Q8IU99]
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== Publication Abstract from PubMed ==
Calcium homeostasis modulators (CALHMs) are voltage-gated, Ca(2+)-inhibited nonselective ion channels that act as major ATP release channels, and have important roles in gustatory signalling and neuronal toxicity(1-3). Dysfunction of CALHMs has previously been linked to neurological disorders(1). Here we present cryo-electron microscopy structures of the human CALHM2 channel in the Ca(2+)-free active or open state and in the ruthenium red (RUR)-bound inhibited state, at resolutions up to 2.7 A. Our work shows that purified CALHM2 channels form both gap junctions and undecameric hemichannels. The protomer shows a mirrored arrangement of the transmembrane domains (helices S1-S4) relative to other channels with a similar topology, such as connexins, innexins and volume-regulated anion channels(4-8). Upon binding to RUR, we observed a contracted pore with notable conformational changes of the pore-lining helix S1, which swings nearly 60 degrees towards the pore axis from a vertical to a lifted position. We propose a two-section gating mechanism in which the S1 helix coarsely adjusts, and the N-terminal helix fine-tunes, the pore size. We identified a RUR-binding site near helix S1 that may stabilize this helix in the lifted conformation, giving rise to channel inhibition. Our work elaborates on the principles of CALHM2 channel architecture and symmetry, and the mechanism that underlies channel inhibition.

The structures and gating mechanism of human calcium homeostasis modulator 2.,Choi W, Clemente N, Sun W, Du J, Lu W Nature. 2019 Dec;576(7785):163-167. doi: 10.1038/s41586-019-1781-3. Epub 2019 Nov, 27. PMID:31776515<ref>PMID:31776515</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 6uiw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Choi W]]
[[Category: Du J]]
[[Category: Lu W]]