View source for 6bcq


==cryo-EM structure of TRPM4 in ATP bound state with long coiled coil at 3.3 angstrom resolution==
<SX load='6bcq' size='340' side='right' viewer='molstar' caption='[[6bcq]], [[Resolution|resolution]] 3.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6bcq]] 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=6BCQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BCQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.25&#8491;</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6bcq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bcq OCA], [https://pdbe.org/6bcq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bcq RCSB], [https://www.ebi.ac.uk/pdbsum/6bcq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bcq ProSAT]</span></td></tr>
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== Function ==
[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> 
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== 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<ref>PMID:29211714</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6bcq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Bai X]]
[[Category: Chen Q]]
[[Category: Guo J]]
[[Category: Jiang Y]]
[[Category: She J]]