View source for 7mbt


==Cryo-EM structure of zebrafish TRPM5 E337A mutant in the presence of 5 mM calcium (low calcium occupancy in the transmembrane domain)==
<StructureSection load='7mbt' size='340' side='right'caption='[[7mbt]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MBT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MBT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=YUV:(25R)-14beta,17beta-spirost-5-en-3beta-ol'>YUV</scene>, <scene name='pdbligand=YUY:(2R)-2-(hydroxymethyl)-4-{[(25R)-10alpha,14beta,17beta-spirost-5-en-3beta-yl]oxy}butyl+4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside'>YUY</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=7mbt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mbt OCA], [https://pdbe.org/7mbt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mbt RCSB], [https://www.ebi.ac.uk/pdbsum/7mbt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mbt ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The Ca(2+)-activated TRPM5 channel plays essential roles in taste perception and insulin secretion. However, the mechanism by which Ca(2+) regulates TRPM5 activity remains elusive. We report cryo-EM structures of the zebrafish TRPM5 in an apo closed state, a Ca(2+)-bound open state, and an antagonist-bound inhibited state. We define two novel ligand binding sites: a Ca(2+) site (CaICD) in the intracellular domain and an antagonist site in the transmembrane domain (TMD). The CaICD site is unique to TRPM5 and has two roles: modulating the voltage dependence and promoting Ca(2+) binding to the CaTMD site, which is conserved throughout TRPM channels. Conformational changes initialized from both Ca(2+) sites cooperatively open the ion-conducting pore. The antagonist NDNA wedges into the space between the S1-S4 domain and pore domain, stabilizing the transmembrane domain in an apo-like closed state. Our results lay the foundation for understanding the voltage-dependent TRPM channels and developing new therapeutic agents.

,  PMID:34168372<ref>PMID:34168372</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 7mbt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Du J]]
[[Category: Haley E]]
[[Category: Lu W]]
[[Category: Ruan Z]]