8grs

From Proteopedia

(Difference between revisions)

Current revision

human TMEM63A

Structural highlights

8grs 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 3.3Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CSCL1_HUMAN The disease is caused by variants affecting the gene represented in this entry.

Function

CSCL1_HUMAN Acts as an osmosensitive calcium-permeable cation channel (PubMed:30382938, PubMed:31587869). Mechanosensitive ion channel that converts mechanical stimuli into a flow of ion (PubMed:30382938, PubMed:31587869, PubMed:37543036).[UniProtKB:Q91YT8]^[1] ^[2] ^[3]

Publication Abstract from PubMed

Mechanosensitive (MS) ion channels are a ubiquitous type of molecular force sensor sensing forces from the surrounding bilayer. The profound structural diversity in these channels suggests that the molecular mechanisms of force sensing follow unique structural blueprints. Here we determine the structures of plant and mammalian OSCA/TMEM63 proteins, allowing us to identify essential elements for mechanotransduction and propose roles for putative bound lipids in OSCA/TMEM63 mechanosensation. Briefly, the central cavity created by the dimer interface couples each subunit and modulates dimeric OSCA/TMEM63 channel mechanosensitivity through the modulating lipids while the cytosolic side of the pore is gated by a plug lipid that prevents the ion permeation. Our results suggest that the gating mechanism of OSCA/TMEM63 channels may combine structural aspects of the 'lipid-gated' mechanism of MscS and TRAAK channels and the calcium-induced gating mechanism of the TMEM16 family, which may provide insights into the structural rearrangements of TMEM16/TMC superfamilies.

A mechanical-coupling mechanism in OSCA/TMEM63 channel mechanosensitivity.,Zhang M, Shan Y, Cox CD, Pei D Nat Commun. 2023 Jul 4;14(1):3943. doi: 10.1038/s41467-023-39688-8. PMID:37402734^[4]

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

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
↑ Zhang M, Shan Y, Cox CD, Pei D. A mechanical-coupling mechanism in OSCA/TMEM63 channel mechanosensitivity. Nat Commun. 2023 Jul 4;14(1):3943. PMID:37402734 doi:10.1038/s41467-023-39688-8

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8grs"

Categories: Homo sapiens | Large Structures | Zhang MF

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[8grs]] 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=8GRS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GRS FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</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=8grs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8grs OCA], [https://pdbe.org/8grs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8grs RCSB], [https://www.ebi.ac.uk/pdbsum/8grs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8grs ProSAT]</span></td></tr>
 </table>
@@ Line 10: / Line 11: @@
 [https://www.uniprot.org/uniprot/CSCL1_HUMAN CSCL1_HUMAN] The disease is caused by variants affecting the gene represented in this entry.
 == Function ==
-[https://www.uniprot.org/uniprot/CSCL1_HUMAN CSCL1_HUMAN] Acts as an osmosensitive calcium-permeable cation channel (PubMed:30382938, PubMed:31587869). Mechanosensitive ion channel that converts mechanical stimuli into a flow of ion (PubMed:30382938, PubMed:31587869).[UniProtKB:Q91YT8]<ref>PMID:30382938</ref> <ref>PMID:31587869</ref>
+[https://www.uniprot.org/uniprot/CSCL1_HUMAN CSCL1_HUMAN] Acts as an osmosensitive calcium-permeable cation channel (PubMed:30382938, PubMed:31587869). Mechanosensitive ion channel that converts mechanical stimuli into a flow of ion (PubMed:30382938, PubMed:31587869, PubMed:37543036).[UniProtKB:Q91YT8]<ref>PMID:30382938</ref> <ref>PMID:31587869</ref> <ref>PMID:37543036</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Mechanosensitive (MS) ion channels are a ubiquitous type of molecular force sensor sensing forces from the surrounding bilayer. The profound structural diversity in these channels suggests that the molecular mechanisms of force sensing follow unique structural blueprints. Here we determine the structures of plant and mammalian OSCA/TMEM63 proteins, allowing us to identify essential elements for mechanotransduction and propose roles for putative bound lipids in OSCA/TMEM63 mechanosensation. Briefly, the central cavity created by the dimer interface couples each subunit and modulates dimeric OSCA/TMEM63 channel mechanosensitivity through the modulating lipids while the cytosolic side of the pore is gated by a plug lipid that prevents the ion permeation. Our results suggest that the gating mechanism of OSCA/TMEM63 channels may combine structural aspects of the 'lipid-gated' mechanism of MscS and TRAAK channels and the calcium-induced gating mechanism of the TMEM16 family, which may provide insights into the structural rearrangements of TMEM16/TMC superfamilies.
+A mechanical-coupling mechanism in OSCA/TMEM63 channel mechanosensitivity.,Zhang M, Shan Y, Cox CD, Pei D Nat Commun. 2023 Jul 4;14(1):3943. doi: 10.1038/s41467-023-39688-8. PMID:37402734<ref>PMID:37402734</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 8grs" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

8grs

From Proteopedia

Current revision

human TMEM63A

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

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