View source for 30kw


==Human Trpm4 at 8 degrees Celsius==
<StructureSection load='30kw' size='340' side='right'caption='[[30kw]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[30kw]] 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=30KW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=30KW 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]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</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=30kw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=30kw OCA], [https://pdbe.org/30kw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=30kw RCSB], [https://www.ebi.ac.uk/pdbsum/30kw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=30kw 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 ==
Transient receptor potential melastatin 4 (TRPM4) is a Ca(2)(+)-activated cation channel whose pharmacology is shaped by its molecular environment. It remains poorly understood how temperature and membrane context influence inhibitor recognition. Here we combine cryo-electron microscopy of membrane-derived vesicles and detergent-solubilized TRPM4 to investigate lipid-associated architecture and binding of the potent anthranilic anilide inhibitor PBA. We find that membrane vesicles preserve a native-like paralipid environment and reveal lipid binding patterns highly similar to those observed in GDN, supporting detergent-solubilized TRPM4 as a structurally relevant system for ligand analysis. Strikingly, PBA occupies distinct binding pockets at 8 square degrees C and 37 square degrees C. At low temperature, PBA binds in a previously described inhibitor pocket formed by S3, S4, the S4-S5 linker and the TRP helix, whereas at physiological temperature it relocates to a distinct site within the S1-S4 domain proximal to the Ca(2)(+) regulatory region. These findings reveal temperature-dependent plasticity in TRPM4 ligand recognition.

Temperature-dependent ligand relocation reveals plasticity of TRPM4 inhibition.,Schneiter D, Rougier JS, Abriel H, Stahlberg H, Ekundayo B bioRxiv [Preprint]. 2026 May 14:2026.05.13.724805. doi: , 10.64898/2026.05.13.724805. PMID:42182356<ref>PMID:42182356</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 30kw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Abriel H]]
[[Category: Ekundayo BE]]
[[Category: Schneiter D]]
[[Category: Stahlberg H]]