7epe: Difference between revisions
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==Crystal structure of mGlu2 bound to NAM563== | ==Crystal structure of mGlu2 bound to NAM563== | ||
<StructureSection load='7epe' size='340' side='right'caption='[[7epe]]' scene=''> | <StructureSection load='7epe' size='340' side='right'caption='[[7epe]], [[Resolution|resolution]] 2.50Å' 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=7EPE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EPE FirstGlance]. <br> | <table><tr><td colspan='2'>[[7epe]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EPE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EPE 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=7epe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7epe OCA], [https://pdbe.org/7epe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7epe RCSB], [https://www.ebi.ac.uk/pdbsum/7epe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7epe 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=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=J9R:4-(1-methylpyrazol-4-yl)-7-[[(2~{S})-2-(trifluoromethyl)morpholin-4-yl]methyl]quinoline-2-carboxamide'>J9R</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=7epe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7epe OCA], [https://pdbe.org/7epe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7epe RCSB], [https://www.ebi.ac.uk/pdbsum/7epe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7epe ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The metabotropic glutamate receptors (mGlus) are involved in the modulation of synaptic transmission and neuronal excitability in the central nervous system(1). These receptors probably exist as both homo- and heterodimers that have unique pharmacological and functional properties(2-4). Here we report four cryo-electron microscopy structures of the human mGlu subtypes mGlu2 and mGlu7, including inactive mGlu2 and mGlu7 homodimers; mGlu2 homodimer bound to an agonist and a positive allosteric modulator; and inactive mGlu2-mGlu7 heterodimer. We observed a subtype-dependent dimerization mode for these mGlus, as a unique dimer interface that is mediated by helix IV (and that is important for limiting receptor activity) exists only in the inactive mGlu2 structure. The structures provide molecular details of the inter- and intra-subunit conformational changes that are required for receptor activation, which distinguish class C G-protein-coupled receptors from those in classes A and B. Furthermore, our structure and functional studies of the mGlu2-mGlu7 heterodimer suggest that the mGlu7 subunit has a dominant role in controlling dimeric association and G-protein activation in the heterodimer. These insights into mGlu homo- and heterodimers highlight the complex landscape of mGlu dimerization and activation. | |||
Structures of human mGlu2 and mGlu7 homo- and heterodimers.,Du J, Wang D, Fan H, Xu C, Tai L, Lin S, Han S, Tan Q, Wang X, Xu T, Zhang H, Chu X, Yi C, Liu P, Wang X, Zhou Y, Pin JP, Rondard P, Liu H, Liu J, Sun F, Wu B, Zhao Q Nature. 2021 Jun;594(7864):589-593. doi: 10.1038/s41586-021-03641-w. Epub 2021, Jun 16. PMID:34135509<ref>PMID:34135509</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7epe" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Du J]] | [[Category: Du, J]] | ||
[[Category: Han S]] | [[Category: Han, S]] | ||
[[Category: Lin S]] | [[Category: Lin, S]] | ||
[[Category: Wang D]] | [[Category: Wang, D]] | ||
[[Category: Wu B]] | [[Category: Wu, B]] | ||
[[Category: Zhao Q]] | [[Category: Zhao, Q]] | ||
[[Category: Gpcr]] | |||
[[Category: Membrane protein]] | |||
Revision as of 13:14, 7 July 2021
Crystal structure of mGlu2 bound to NAM563Crystal structure of mGlu2 bound to NAM563
Structural highlights
Publication Abstract from PubMedThe metabotropic glutamate receptors (mGlus) are involved in the modulation of synaptic transmission and neuronal excitability in the central nervous system(1). These receptors probably exist as both homo- and heterodimers that have unique pharmacological and functional properties(2-4). Here we report four cryo-electron microscopy structures of the human mGlu subtypes mGlu2 and mGlu7, including inactive mGlu2 and mGlu7 homodimers; mGlu2 homodimer bound to an agonist and a positive allosteric modulator; and inactive mGlu2-mGlu7 heterodimer. We observed a subtype-dependent dimerization mode for these mGlus, as a unique dimer interface that is mediated by helix IV (and that is important for limiting receptor activity) exists only in the inactive mGlu2 structure. The structures provide molecular details of the inter- and intra-subunit conformational changes that are required for receptor activation, which distinguish class C G-protein-coupled receptors from those in classes A and B. Furthermore, our structure and functional studies of the mGlu2-mGlu7 heterodimer suggest that the mGlu7 subunit has a dominant role in controlling dimeric association and G-protein activation in the heterodimer. These insights into mGlu homo- and heterodimers highlight the complex landscape of mGlu dimerization and activation. Structures of human mGlu2 and mGlu7 homo- and heterodimers.,Du J, Wang D, Fan H, Xu C, Tai L, Lin S, Han S, Tan Q, Wang X, Xu T, Zhang H, Chu X, Yi C, Liu P, Wang X, Zhou Y, Pin JP, Rondard P, Liu H, Liu J, Sun F, Wu B, Zhao Q Nature. 2021 Jun;594(7864):589-593. doi: 10.1038/s41586-021-03641-w. Epub 2021, Jun 16. PMID:34135509[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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