7mbu: Difference between revisions
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<StructureSection load='7mbu' size='340' side='right'caption='[[7mbu]]' scene=''> | <StructureSection load='7mbu' size='340' side='right'caption='[[7mbu]]' 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=7MBU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MBU FirstGlance]. <br> | <table><tr><td colspan='2'>[[7mbu]] 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=7MBU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MBU 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=7mbu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mbu OCA], [https://pdbe.org/7mbu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mbu RCSB], [https://www.ebi.ac.uk/pdbsum/7mbu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mbu 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=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=7mbu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mbu OCA], [https://pdbe.org/7mbu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mbu RCSB], [https://www.ebi.ac.uk/pdbsum/7mbu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mbu 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 7mbu" 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]] | |||
Latest revision as of 13:53, 28 July 2021
Cryo-EM structure of zebrafish TRPM5 E337A mutant in the presence of 5 mM calcium (high calcium occupancy in the transmembrane domain)Cryo-EM structure of zebrafish TRPM5 E337A mutant in the presence of 5 mM calcium (high calcium occupancy in the transmembrane domain)
Structural highlights
Publication Abstract from PubMedThe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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