View source for 5wp6


==Cryo-EM structure of a human TRPM4 channel in complex with calcium and decavanadate==
<SX load='5wp6' size='340' side='right' viewer='molstar' caption='[[5wp6]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5wp6]] is a 4 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=5WP6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WP6 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]] 3.8&#8491;</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=5wp6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wp6 OCA], [https://pdbe.org/5wp6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wp6 RCSB], [https://www.ebi.ac.uk/pdbsum/5wp6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wp6 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TRPM4_HUMAN TRPM4_HUMAN] Familial progressive cardiac conduction defect;Brugada syndrome. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/TRPM4_HUMAN TRPM4_HUMAN] 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.<ref>PMID:12015988</ref> <ref>PMID:12799367</ref> <ref>PMID:15121803</ref> <ref>PMID:15472118</ref> <ref>PMID:15550671</ref> <ref>PMID:16806463</ref> <ref>PMID:20625999</ref> <ref>PMID:20656926</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ca(2+)-activated, non-selective (CAN) ion channels sense increases of the intracellular Ca(2+) concentration, producing a flux of Na(+) and/or K(+) ions that depolarizes the cell, thus modulating cellular Ca(2+) entry. CAN channels are involved in cellular responses such as neuronal bursting activity and cardiac rhythm. Here we report the electron cryo-microscopy structure of the most widespread CAN channel, human TRPM4, bound to the agonist Ca(2+) and the modulator decavanadate. Four cytosolic C-terminal domains form an umbrella-like structure with a coiled-coil domain for the 'pole' and four helical 'ribs' spanning the N-terminal TRPM homology regions (MHRs), thus holding four subunits in a crown-like architecture. We observed two decavanadate-binding sites, one in the C-terminal domain and another in the intersubunit MHR interface. A glutamine in the selectivity filter may be an important determinant of monovalent selectivity. Our structure provides new insights into the function and pharmacology of both the CAN and the TRPM families.

Electron cryo-microscopy structure of a human TRPM4 channel.,Winkler PA, Huang Y, Sun W, Du J, Lu W Nature. 2017 Dec 14;552(7684):200-204. doi: 10.1038/nature24674. Epub 2017 Dec 6. PMID:29211723<ref>PMID:29211723</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5wp6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</SX>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Du J]]
[[Category: Huang Y]]
[[Category: Lu W]]
[[Category: Sun W]]
[[Category: Winkler PA]]