View source for 8tal


==TMEM16F, with Calcium and PIP2, no inhibitor, Cl1==
<StructureSection load='8tal' size='340' side='right'caption='[[8tal]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8tal]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8TAL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8TAL 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]] 3.2&#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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=8tal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8tal OCA], [https://pdbe.org/8tal PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8tal RCSB], [https://www.ebi.ac.uk/pdbsum/8tal PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8tal ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ANO6_MOUSE ANO6_MOUSE] Small-conductance calcium-activated nonselective cation (SCAN) channel which acts as a regulator of phospholipid scrambling in platelets, osteoblasts and fetal thymocytes. Phospholipid scrambling results in surface exposure of phosphatidylserine which in platelets is essential to trigger the clotting system whereas in osteoblasts is essential for the deposition of hydroxyapatite during bone mineralization. Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylserine, phosphatidylcholine and galactosylceramide. Can generate outwardly rectifying chloride channel currents in airway epithelial cells and Jurkat T lymphocytes.<ref>PMID:21107324</ref> <ref>PMID:21908539</ref> <ref>PMID:22936354</ref> <ref>PMID:23021219</ref> <ref>PMID:23532839</ref> 
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== Publication Abstract from PubMed ==
The dual functions of TMEM16F as Ca(2+)-activated ion channel and lipid scramblase raise intriguing questions regarding their molecular basis. Intrigued by the ability of the FDA-approved drug niclosamide to inhibit TMEM16F-dependent syncytia formation induced by SARS-CoV-2, we examined cryo-EM structures of TMEM16F with or without bound niclosamide or 1PBC, a known blocker of TMEM16A Ca(2+)-activated Cl(-) channel. Here, we report evidence for a lipid scrambling pathway along a groove harboring a lipid trail outside the ion permeation pore. This groove contains the binding pocket for niclosamide and 1PBC. Mutations of two residues in this groove specifically affect lipid scrambling. Whereas mutations of some residues in the binding pocket of niclosamide and 1PBC reduce their inhibition of TMEM16F-mediated Ca(2+) influx and PS exposure, other mutations preferentially affect the ability of niclosamide and/or 1PBC to inhibit TMEM16F-mediated PS exposure, providing further support for separate pathways for ion permeation and lipid scrambling.

Identification of a drug binding pocket in TMEM16F calcium-activated ion channel and lipid scramblase.,Feng S, Puchades C, Ko J, Wu H, Chen Y, Figueroa EE, Gu S, Han TW, Ho B, Cheng T, Li J, Shoichet B, Jan YN, Cheng Y, Jan LY Nat Commun. 2023 Aug 12;14(1):4874. doi: 10.1038/s41467-023-40410-x. PMID:37573365<ref>PMID:37573365</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 8tal" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Cheng Y]]
[[Category: Feng S]]
[[Category: Wu H]]