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6p47

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Revision as of 12:20, 18 December 2019

Cryo-EM structure of TMEM16F in digitonin without calcium

Structural highlights

6p47 is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	Ano6, Tmem16f (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

As a Ca(2+)-activated lipid scramblase and ion channel that mediates Ca(2+) influx, TMEM16F relies on both functions to facilitate extracellular vesicle generation, blood coagulation, and bone formation. How a bona fide ion channel scrambles lipids remains elusive. Our structural analyses revealed the coexistence of an intact channel pore and PIP2-dependent protein conformation changes leading to membrane distortion. Correlated to the extent of membrane distortion, many tightly bound lipids are slanted. Structure-based mutagenesis studies further reveal that neutralization of some lipid-binding residues or those near membrane distortion specifically alters the onset of lipid scrambling, but not Ca(2+) influx, thus identifying features outside of channel pore that are important for lipid scrambling. Together, our studies demonstrate that membrane distortion does not require open hydrophilic grooves facing the membrane interior and provide further evidence to suggest separate pathways for lipid scrambling and ion permeation.

Cryo-EM Studies of TMEM16F Calcium-Activated Ion Channel Suggest Features Important for Lipid Scrambling.,Feng S, Dang S, Han TW, Ye W, Jin P, Cheng T, Li J, Jan YN, Jan LY, Cheng Y Cell Rep. 2019 Jul 9;28(2):567-579.e4. doi: 10.1016/j.celrep.2019.06.023. PMID:31291589^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Suzuki J, Umeda M, Sims PJ, Nagata S. Calcium-dependent phospholipid scrambling by TMEM16F. Nature. 2010 Dec 9;468(7325):834-8. doi: 10.1038/nature09583. Epub 2010 Nov 24. PMID:21107324 doi:http://dx.doi.org/10.1038/nature09583
↑ Kunzelmann K, Schreiber R, Kmit A, Jantarajit W, Martins JR, Faria D, Kongsuphol P, Ousingsawat J, Tian Y. Expression and function of epithelial anoctamins. Exp Physiol. 2012 Feb;97(2):184-92. doi: 10.1113/expphysiol.2011.058206. Epub, 2011 Sep 9. PMID:21908539 doi:http://dx.doi.org/10.1113/expphysiol.2011.058206
↑ Ehlen HW, Chinenkova M, Moser M, Munter HM, Krause Y, Gross S, Brachvogel B, Wuelling M, Kornak U, Vortkamp A. Inactivation of anoctamin-6/Tmem16f, a regulator of phosphatidylserine scrambling in osteoblasts, leads to decreased mineral deposition in skeletal tissues. J Bone Miner Res. 2013 Feb;28(2):246-59. doi: 10.1002/jbmr.1751. PMID:22936354 doi:http://dx.doi.org/10.1002/jbmr.1751
↑ Yang H, Kim A, David T, Palmer D, Jin T, Tien J, Huang F, Cheng T, Coughlin SR, Jan YN, Jan LY. TMEM16F forms a Ca2+-activated cation channel required for lipid scrambling in platelets during blood coagulation. Cell. 2012 Sep 28;151(1):111-22. doi: 10.1016/j.cell.2012.07.036. PMID:23021219 doi:http://dx.doi.org/10.1016/j.cell.2012.07.036
↑ Suzuki J, Fujii T, Imao T, Ishihara K, Kuba H, Nagata S. Calcium-dependent phospholipid scramblase activity of TMEM16 protein family members. J Biol Chem. 2013 May 10;288(19):13305-16. doi: 10.1074/jbc.M113.457937. Epub, 2013 Mar 26. PMID:23532839 doi:http://dx.doi.org/10.1074/jbc.M113.457937
↑ Feng S, Dang S, Han TW, Ye W, Jin P, Cheng T, Li J, Jan YN, Jan LY, Cheng Y. Cryo-EM Studies of TMEM16F Calcium-Activated Ion Channel Suggest Features Important for Lipid Scrambling. Cell Rep. 2019 Jul 9;28(2):567-579.e4. doi: 10.1016/j.celrep.2019.06.023. PMID:31291589 doi:http://dx.doi.org/10.1016/j.celrep.2019.06.023

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6p47"

@@ Line 3: / Line 3: @@
 <StructureSection load='6p47' size='340' side='right'caption='[[6p47]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6p47]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P47 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6P47 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6p47]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P47 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6P47 FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6p47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p47 OCA], [http://pdbe.org/6p47 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p47 RCSB], [http://www.ebi.ac.uk/pdbsum/6p47 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p47 ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ano6, Tmem16f ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6p47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p47 OCA], [http://pdbe.org/6p47 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p47 RCSB], [http://www.ebi.ac.uk/pdbsum/6p47 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p47 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 23: @@
 </StructureSection>
 [[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Cheng, T]]
 [[Category: Cheng, Y]]

6p47

From Proteopedia

Revision as of 12:20, 18 December 2019

Cryo-EM structure of TMEM16F in digitonin without calcium

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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