View source for 9y2a


==Cryo-EM structure of the human TRPM4 channel in complex with calcium and DAB at 37 degrees Celsius==
<StructureSection load='9y2a' size='340' side='right'caption='[[9y2a]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9y2a]] 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=9Y2A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9Y2A 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]] 3.3&#8491;</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>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=9y2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9y2a OCA], [https://pdbe.org/9y2a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9y2a RCSB], [https://www.ebi.ac.uk/pdbsum/9y2a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9y2a 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 --&gt; VGCC/NCX --&gt; 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9y2a" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Jinhong H]]
[[Category: Juan D]]
[[Category: Wei L]]