7mbs: Difference between revisions
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<StructureSection load='7mbs' size='340' side='right'caption='[[7mbs]]' scene=''> | <StructureSection load='7mbs' size='340' side='right'caption='[[7mbs]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MBS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MBS FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <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='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=CA:CALCIUM+ION'>CA</scene>, <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=7mbs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mbs OCA], [https://pdbe.org/7mbs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mbs RCSB], [https://www.ebi.ac.uk/pdbsum/7mbs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mbs ProSAT]</span></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=7mbs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mbs OCA], [https://pdbe.org/7mbs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mbs RCSB], [https://www.ebi.ac.uk/pdbsum/7mbs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mbs ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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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. | 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Du | [[Category: Du J]] | ||
[[Category: Haley | [[Category: Haley E]] | ||
[[Category: Lu | [[Category: Lu W]] | ||
[[Category: Ruan | [[Category: Ruan Z]] | ||
