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6bco

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cryo-EM structure of TRPM4 in ATP bound state with short coiled coil at 2.9 angstrom resolution

6bco, resolution 2.88Å

Structural highlights

6bco is a 4 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.
Ligands:
Related:	6bcj, 6bcl, 6bcq
Gene:	Trpm4, Ltrpc4 (LK3 transgenic mice)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

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/6bco"

@@ Line 3: / Line 3: @@
 <SX load='6bco' size='340' side='right' viewer='molstar' caption='[[6bco]], [[Resolution|resolution]] 2.88&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6bco]] 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=6BCO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BCO FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6bco]] 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=6BCO OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6BCO FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6bcj|6bcj]], [[6bcl|6bcl]], [[6bcq|6bcq]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bco OCA], [http://pdbe.org/6bco PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bco RCSB], [http://www.ebi.ac.uk/pdbsum/6bco PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bco 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=6bco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bco OCA], [http://pdbe.org/6bco PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bco RCSB], [http://www.ebi.ac.uk/pdbsum/6bco PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bco ProSAT]</span></td></tr>
 </table>
 == Function ==

6bco

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Current revision

cryo-EM structure of TRPM4 in ATP bound state with short coiled coil at 2.9 angstrom resolution

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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