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| | <SX load='6bcl' size='340' side='right' viewer='molstar' caption='[[6bcl]], [[Resolution|resolution]] 3.54Å' scene=''> | | <SX load='6bcl' size='340' side='right' viewer='molstar' caption='[[6bcl]], [[Resolution|resolution]] 3.54Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bcl]] is a 4 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=6BCL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6BCL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bcl]] is a 4 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=6BCL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BCL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 3.54Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6bcj|6bcj]], [[6bcq|6bcq]], [[6bco|6bco]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Trpm4, Ltrpc4 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=6bcl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bcl OCA], [https://pdbe.org/6bcl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bcl RCSB], [https://www.ebi.ac.uk/pdbsum/6bcl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bcl ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6bcl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bcl OCA], [http://pdbe.org/6bcl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bcl RCSB], [http://www.ebi.ac.uk/pdbsum/6bcl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bcl ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TRPM4_MOUSE TRPM4_MOUSE]] Calcium-activated non selective (CAN) cation channel that mediates membrane depolarization. While it is activated by increase in intracellular Ca(2+), it is impermeable to it. Mediates transport of monovalent cations (Na(+) > K(+) > Cs(+) > Li(+)), leading to depolarize the membrane. It thereby plays a central role in cadiomyocytes, neurons from entorhinal cortex, dorsal root and vomeronasal neurons, endocrine pancreas cells, kidney epithelial cells, cochlea hair cells etc. Participates in T-cell activation by modulating Ca(2+) oscillations after T lymphocyte activation, which is required for NFAT-dependent IL2 production. Involved in myogenic constriction of cerebral arteries. Controls insulin secretion in pancreatic beta-cells. May also be involved in pacemaking or could cause irregular electrical activity under conditions of Ca(2+) overload. Affects T-helper 1 (Th1) and T-helper 2 (Th2) cell motility and cytokine production through differential regulation of calcium signaling and NFATC1 localization. Enhances cell proliferation through up-regulation of the beta-catenin signaling pathway (By similarity). Essential for the migration but not the maturation of dendritic cells.<ref>PMID:17188667</ref> <ref>PMID:18758465</ref> | + | [https://www.uniprot.org/uniprot/TRPM4_MOUSE TRPM4_MOUSE] Calcium-activated non selective (CAN) cation channel that mediates membrane depolarization. While it is activated by increase in intracellular Ca(2+), it is impermeable to it. Mediates transport of monovalent cations (Na(+) > K(+) > Cs(+) > Li(+)), leading to depolarize the membrane. It thereby plays a central role in cadiomyocytes, neurons from entorhinal cortex, dorsal root and vomeronasal neurons, endocrine pancreas cells, kidney epithelial cells, cochlea hair cells etc. Participates in T-cell activation by modulating Ca(2+) oscillations after T lymphocyte activation, which is required for NFAT-dependent IL2 production. Involved in myogenic constriction of cerebral arteries. Controls insulin secretion in pancreatic beta-cells. May also be involved in pacemaking or could cause irregular electrical activity under conditions of Ca(2+) overload. Affects T-helper 1 (Th1) and T-helper 2 (Th2) cell motility and cytokine production through differential regulation of calcium signaling and NFATC1 localization. Enhances cell proliferation through up-regulation of the beta-catenin signaling pathway (By similarity). Essential for the migration but not the maturation of dendritic cells.<ref>PMID:17188667</ref> <ref>PMID:18758465</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </SX> | | </SX> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Bai, X]] | + | [[Category: Bai X]] |
| - | [[Category: Chen, Q]] | + | [[Category: Chen Q]] |
| - | [[Category: Guo, J]] | + | [[Category: Guo J]] |
| - | [[Category: Jiang, Y]] | + | [[Category: Jiang Y]] |
| - | [[Category: She, J]] | + | [[Category: She J]] |
| - | [[Category: Ion channel]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
Function
TRPM4_MOUSE Calcium-activated non selective (CAN) cation channel that mediates membrane depolarization. While it is activated by increase in intracellular Ca(2+), it is impermeable to it. Mediates transport of monovalent cations (Na(+) > K(+) > Cs(+) > Li(+)), leading to depolarize the membrane. It thereby plays a central role in cadiomyocytes, neurons from entorhinal cortex, dorsal root and vomeronasal neurons, endocrine pancreas cells, kidney epithelial cells, cochlea hair cells etc. Participates in T-cell activation by modulating Ca(2+) oscillations after T lymphocyte activation, which is required for NFAT-dependent IL2 production. Involved in myogenic constriction of cerebral arteries. Controls insulin secretion in pancreatic beta-cells. May also be involved in pacemaking or could cause irregular electrical activity under conditions of Ca(2+) overload. Affects T-helper 1 (Th1) and T-helper 2 (Th2) cell motility and cytokine production through differential regulation of calcium signaling and NFATC1 localization. Enhances cell proliferation through up-regulation of the beta-catenin signaling pathway (By similarity). Essential for the migration but not the maturation of dendritic cells.[1] [2]
Publication Abstract from PubMed
TRPM4 is a calcium-activated, phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) -modulated, non-selective cation channel that belongs to the family of melastatin-related transient receptor potential (TRPM) channels. Here we present the electron cryo-microscopy structures of the mouse TRPM4 channel with and without ATP. TRPM4 consists of multiple transmembrane and cytosolic domains, which assemble into a three-tiered architecture. The N-terminal nucleotide-binding domain and the C-terminal coiled-coil participate in the tetrameric assembly of the channel; ATP binds at the nucleotide-binding domain and inhibits channel activity. TRPM4 has an exceptionally wide filter but is only permeable to monovalent cations; filter residue Gln973 is essential in defining monovalent selectivity. The S1-S4 domain and the post-S6 TRP domain form the central gating apparatus that probably houses the Ca(2+)- and PtdIns(4,5)P2-binding sites. These structures provide an essential starting point for elucidating the complex gating mechanisms of TRPM4 and reveal the molecular architecture of the TRPM family.
Structures of the calcium-activated, non-selective cation channel TRPM4.,Guo J, She J, Zeng W, Chen Q, Bai XC, Jiang Y Nature. 2017 Dec 14;552(7684):205-209. doi: 10.1038/nature24997. Epub 2017 Dec 6. PMID:29211714[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Demion M, Bois P, Launay P, Guinamard R. TRPM4, a Ca2+-activated nonselective cation channel in mouse sino-atrial node cells. Cardiovasc Res. 2007 Feb 1;73(3):531-8. doi: 10.1016/j.cardiores.2006.11.023., Epub 2006 Nov 22. PMID:17188667 doi:http://dx.doi.org/10.1016/j.cardiores.2006.11.023
- ↑ Barbet G, Demion M, Moura IC, Serafini N, Leger T, Vrtovsnik F, Monteiro RC, Guinamard R, Kinet JP, Launay P. The calcium-activated nonselective cation channel TRPM4 is essential for the migration but not the maturation of dendritic cells. Nat Immunol. 2008 Oct;9(10):1148-56. doi: 10.1038/ni.1648. Epub 2008 Aug 31. PMID:18758465 doi:http://dx.doi.org/10.1038/ni.1648
- ↑ Guo J, She J, Zeng W, Chen Q, Bai XC, Jiang Y. Structures of the calcium-activated, non-selective cation channel TRPM4. Nature. 2017 Dec 14;552(7684):205-209. doi: 10.1038/nature24997. Epub 2017 Dec 6. PMID:29211714 doi:http://dx.doi.org/10.1038/nature24997
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