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7mbv
From Proteopedia
(Difference between revisions)
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==Cryo-EM structure of zebrafish TRPM5 in the presence of 5 mM calcium and 0.5 mM NDNA== | ==Cryo-EM structure of zebrafish TRPM5 in the presence of 5 mM calcium and 0.5 mM NDNA== | ||
| - | <StructureSection load='7mbv' size='340' side='right'caption='[[7mbv]]' scene=''> | + | <StructureSection load='7mbv' size='340' side='right'caption='[[7mbv]], [[Resolution|resolution]] 2.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MBV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MBV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7mbv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MBV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MBV FirstGlance]. <br> |
| - | </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=7mbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mbv OCA], [https://pdbe.org/7mbv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mbv RCSB], [https://www.ebi.ac.uk/pdbsum/7mbv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mbv ProSAT]</span></td></tr> | + | </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=YUS:N-[(E)-(3,4-dimethoxyphenyl)methylidene]-2-(naphthalen-1-yl)acetohydrazide'>YUS</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">trpm5, TRPM5 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</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=7mbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mbv OCA], [https://pdbe.org/7mbv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mbv RCSB], [https://www.ebi.ac.uk/pdbsum/7mbv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mbv ProSAT]</span></td></tr> | ||
</table> | </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> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7mbv" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Brachidanio rerio]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Du J]] | + | [[Category: Du, J]] |
| - | [[Category: Haley E]] | + | [[Category: Haley, E]] |
| - | [[Category: Lu W]] | + | [[Category: Lu, W]] |
| - | [[Category: Ruan Z]] | + | [[Category: Ruan, Z]] |
| + | [[Category: Ion channel]] | ||
| + | [[Category: Transport protein]] | ||
| + | [[Category: Trp channel]] | ||
Current revision
Cryo-EM structure of zebrafish TRPM5 in the presence of 5 mM calcium and 0.5 mM NDNA
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