9y2b: Difference between revisions
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==Cryo-EM structure of the human TRPM4 channel in complex with EGTA and DAB at 37 degrees Celsius== | |||
<StructureSection load='9y2b' size='340' side='right'caption='[[9y2b]], [[Resolution|resolution]] 3.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9y2b]] 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=9Y2B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9Y2B 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]] 3.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1CR0:4,4-[(pyridin-2-yl)methylene]diphenol'>A1CR0</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=9y2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9y2b OCA], [https://pdbe.org/9y2b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9y2b RCSB], [https://www.ebi.ac.uk/pdbsum/9y2b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9y2b ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Imbalance in intestinal fluid homeostasis leads to nutrient malabsorption, intestinal tissue destruction, and systemic inflammation. Transient receptor potential melastatin 4 (TRPM4) is a calcium-activated, non-selective monovalent cation channel converting chemical signals (Ca(2+)) into electrical signals (membrane depolarization). Here, we show the TRPM4 channel as a direct target of bisacodyl (BIC), a widely used clinical drug for chronic constipation management, and its active metabolite, deacetyl bisacodyl (DAB). DAB-induced laxative effects are abolished in global and intestinal epithelium-specific TRPM4-knockout mice, establishing the essential role of TRPM4 in intestinal fluid regulation. Furthermore, our structural work reveals DAB bound to an uncharacterized pocket, marking it as a non-Ca(2+) TRPM4 agonist and unveiling a noncanonical Ca(2+)-independent activation mechanism. Additionally, we delineate a signaling axis, TRPM4 --> VGCC/NCX --> ANO1, that governs ion homeostasis in the epithelium. Together, these findings establish TRPM4 as a key regulator of intestinal fluid balance and reveal its noncanonical calcium-independent activation as a therapeutic strategy for constipation. | |||
Noncanonical calcium-independent TRPM4 activation governs intestinal fluid homeostasis.,Liu Y, Hu J, Xue C, Huang W, Ievleva S, Lu W, Du J, Cao Z Nat Commun. 2026 Jan 8;17(1):1253. doi: 10.1038/s41467-025-68014-7. PMID:41507162<ref>PMID:41507162</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9y2b" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Jinhong H]] | |||
[[Category: Juan D]] | |||
[[Category: Wei L]] | |||
Latest revision as of 19:35, 10 February 2026
Cryo-EM structure of the human TRPM4 channel in complex with EGTA and DAB at 37 degrees Celsius
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