9wxv: Difference between revisions

Latest revision as of 07:32, 11 February 2026

Cryo-EM structure of TMEM63A-digitonin-cholesterol

Structural highlights

9wxv is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 4.4Å
Ligands:	CLR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

TM63A_HUMAN The disease is caused by variants affecting the gene represented in this entry.

Function

TM63A_HUMAN Mechanosensitive cation channel with low conductance and high activation threshold (PubMed:30382938, PubMed:31587869, PubMed:37543036). In contrast to TMEM63B, does not show phospholipid scramblase activity (PubMed:39716028). Acts as a regulator of lysosomal morphology by mediating lysosomal mechanosensitivity (By similarity). Important for the baby's first breath and respiration throughout life (PubMed:38127458). Upon lung inflation conducts cation currents in alveolar type 1 and 2 cells triggering lamellar body exocytosis and surfactant secretion into airspace (PubMed:38127458). Also acts as an osmosensitive cation channel preferentially activated by hypotonic stress (By similarity).[UniProtKB:Q91YT8]^[1] ^[2] ^[3] ^[4] ^[5]

References

↑ Murthy SE, Dubin AE, Whitwam T, Jojoa-Cruz S, Cahalan SM, Mousavi SAR, Ward AB, Patapoutian A. OSCA/TMEM63 are an Evolutionarily Conserved Family of Mechanically Activated Ion Channels. Elife. 2018 Nov 1;7:e41844. PMID:30382938 doi:10.7554/eLife.41844
↑ Yan H, Helman G, Murthy SE, Ji H, Crawford J, Kubisiak T, Bent SJ, Xiao J, Taft RJ, Coombs A, Wu Y, Pop A, Li D, de Vries LS, Jiang Y, Salomons GS, van der Knaap MS, Patapoutian A, Simons C, Burmeister M, Wang J, Wolf NI. Heterozygous Variants in the Mechanosensitive Ion Channel TMEM63A Result in Transient Hypomyelination during Infancy. Am J Hum Genet. 2019 Nov 7;105(5):996-1004. PMID:31587869 doi:10.1016/j.ajhg.2019.09.011
↑ Zheng W, Rawson S, Shen Z, Tamilselvan E, Smith HE, Halford J, Shen C, Murthy SE, Ulbrich MH, Sotomayor M, Fu TM, Holt JR. TMEM63 proteins function as monomeric high-threshold mechanosensitive ion channels. Neuron. 2023 Jul 28:S0896-6273(23)00512-3. PMID:37543036 doi:10.1016/j.neuron.2023.07.006
↑ Chen GL, Li JY, Chen X, Liu JW, Zhang Q, Liu JY, Wen J, Wang N, Lei M, Wei JP, Yi L, Li JJ, Ling YP, Yi HQ, Hu Z, Duan J, Zhang J, Zeng B. Mechanosensitive channels TMEM63A and TMEM63B mediate lung inflation-induced surfactant secretion. J Clin Invest. 2024 Dec 21;134(5):e174508. PMID:38127458 doi:10.1172/JCI174508
↑ Miyata Y, Nishimura M, Nagata A, Jing X, Sultan CS, Kuribayashi R, Takahashi K, Lee Y, Nishizawa T, Segawa K. Membrane structure-responsive lipid scramblase activity of the TMEM63/OSCA family. FEBS Lett. 2025 Mar;599(5):656-666. PMID:39716028 doi:10.1002/1873-3468.15084

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Murthy SE, Dubin AE, Whitwam T, Jojoa-Cruz S, Cahalan SM, Mousavi SAR, Ward AB, Patapoutian A. OSCA/TMEM63 are an Evolutionarily Conserved Family of Mechanically Activated Ion Channels. Elife. 2018 Nov 1;7:e41844. PMID:30382938 doi:10.7554/eLife.41844

[2] Yan H, Helman G, Murthy SE, Ji H, Crawford J, Kubisiak T, Bent SJ, Xiao J, Taft RJ, Coombs A, Wu Y, Pop A, Li D, de Vries LS, Jiang Y, Salomons GS, van der Knaap MS, Patapoutian A, Simons C, Burmeister M, Wang J, Wolf NI. Heterozygous Variants in the Mechanosensitive Ion Channel TMEM63A Result in Transient Hypomyelination during Infancy. Am J Hum Genet. 2019 Nov 7;105(5):996-1004. PMID:31587869 doi:10.1016/j.ajhg.2019.09.011

[3] Zheng W, Rawson S, Shen Z, Tamilselvan E, Smith HE, Halford J, Shen C, Murthy SE, Ulbrich MH, Sotomayor M, Fu TM, Holt JR. TMEM63 proteins function as monomeric high-threshold mechanosensitive ion channels. Neuron. 2023 Jul 28:S0896-6273(23)00512-3. PMID:37543036 doi:10.1016/j.neuron.2023.07.006

[4] Chen GL, Li JY, Chen X, Liu JW, Zhang Q, Liu JY, Wen J, Wang N, Lei M, Wei JP, Yi L, Li JJ, Ling YP, Yi HQ, Hu Z, Duan J, Zhang J, Zeng B. Mechanosensitive channels TMEM63A and TMEM63B mediate lung inflation-induced surfactant secretion. J Clin Invest. 2024 Dec 21;134(5):e174508. PMID:38127458 doi:10.1172/JCI174508

[5] Miyata Y, Nishimura M, Nagata A, Jing X, Sultan CS, Kuribayashi R, Takahashi K, Lee Y, Nishizawa T, Segawa K. Membrane structure-responsive lipid scramblase activity of the TMEM63/OSCA family. FEBS Lett. 2025 Mar;599(5):656-666. PMID:39716028 doi:10.1002/1873-3468.15084

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9wxv is ON HOLD  until Paper Publication
+==Cryo-EM structure of TMEM63A-digitonin-cholesterol==
+<StructureSection load='9wxv' size='340' side='right'caption='[[9wxv]], [[Resolution|resolution]] 4.40&Aring;' scene=''>
-Authors:
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9wxv]] is a 1 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=9WXV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9WXV FirstGlance]. <br>
-Description:
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.4&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</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=9wxv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9wxv OCA], [https://pdbe.org/9wxv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9wxv RCSB], [https://www.ebi.ac.uk/pdbsum/9wxv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9wxv ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/TM63A_HUMAN TM63A_HUMAN] The disease is caused by variants affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/TM63A_HUMAN TM63A_HUMAN] Mechanosensitive cation channel with low conductance and high activation threshold (PubMed:30382938, PubMed:31587869, PubMed:37543036). In contrast to TMEM63B, does not show phospholipid scramblase activity (PubMed:39716028). Acts as a regulator of lysosomal morphology by mediating lysosomal mechanosensitivity (By similarity). Important for the baby's first breath and respiration throughout life (PubMed:38127458). Upon lung inflation conducts cation currents in alveolar type 1 and 2 cells triggering lamellar body exocytosis and surfactant secretion into airspace (PubMed:38127458). Also acts as an osmosensitive cation channel preferentially activated by hypotonic stress (By similarity).[UniProtKB:Q91YT8]<ref>PMID:30382938</ref> <ref>PMID:31587869</ref> <ref>PMID:37543036</ref> <ref>PMID:38127458</ref> <ref>PMID:39716028</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Cheng D]]
+[[Category: Corry B]]
+[[Category: Cox DC]]
+[[Category: Han Y]]
+[[Category: Ju L]]
+[[Category: Lin Y]]
+[[Category: Wang H]]
+[[Category: Zhang Y]]
+[[Category: Zhou Z]]

9wxv: Difference between revisions

Latest revision as of 07:32, 11 February 2026

Cryo-EM structure of TMEM63A-digitonin-cholesterol

Structural highlights

Disease

Function

References

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