7mbr: Difference between revisions
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New page: '''Unreleased structure''' The entry 7mbr is ON HOLD Authors: Ruan, Z., Lu, W., Du, J., Haley, E. Description: Cryo-EM structure of zebrafish TRPM5 in the presence of 6 uM calcium (apo... |
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The | ==Cryo-EM structure of zebrafish TRPM5 in the presence of 6 uM calcium (apo state)== | ||
<StructureSection load='7mbr' size='340' side='right'caption='[[7mbr]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MBR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MBR 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=7mbr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mbr OCA], [https://pdbe.org/7mbr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mbr RCSB], [https://www.ebi.ac.uk/pdbsum/7mbr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mbr ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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. | |||
Structures of the TRPM5 channel elucidate mechanisms of activation and inhibition.,Ruan Z, Haley E, Orozco IJ, Sabat M, Myers R, Roth R, Du J, Lu W Nat Struct Mol Biol. 2021 Jun 24. pii: 10.1038/s41594-021-00607-4. doi:, 10.1038/s41594-021-00607-4. PMID:34168372<ref>PMID:34168372</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7mbr" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Du J]] | |||
[[Category: Haley E]] | |||
[[Category: Lu W]] | |||
[[Category: Ruan Z]] | |||
