7epa: Difference between revisions
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==Cryo-EM structure of inactive mGlu2 homodimer== | ==Cryo-EM structure of inactive mGlu2 homodimer== | ||
<StructureSection load='7epa' size='340' side='right'caption='[[7epa]]' scene=''> | <StructureSection load='7epa' size='340' side='right'caption='[[7epa]], [[Resolution|resolution]] 3.60Å' 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=7EPA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EPA FirstGlance]. <br> | <table><tr><td colspan='2'>[[7epa]] is a 2 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=7EPA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EPA 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=7epa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7epa OCA], [https://pdbe.org/7epa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7epa RCSB], [https://www.ebi.ac.uk/pdbsum/7epa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7epa ProSAT]</span></td></tr> | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRM2, GPRC1B, MGLUR2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=7epa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7epa OCA], [https://pdbe.org/7epa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7epa RCSB], [https://www.ebi.ac.uk/pdbsum/7epa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7epa ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/GRM2_HUMAN GRM2_HUMAN]] G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. May mediate suppression of neurotransmission or may be involved in synaptogenesis or synaptic stabilization.<ref>PMID:18297054</ref> <ref>PMID:22300836</ref> <ref>PMID:23129762</ref> <ref>PMID:7620613</ref> | |||
<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 7epa" 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: Fan H]] | [[Category: Fan, H]] | ||
[[Category: Han S]] | [[Category: Han, S]] | ||
[[Category: Lin S]] | [[Category: Lin, S]] | ||
[[Category: Sun F]] | [[Category: Sun, F]] | ||
[[Category: Tai L]] | [[Category: Tai, L]] | ||
[[Category: Wang D]] | [[Category: Wang, D]] | ||
[[Category: Wu B]] | [[Category: Wu, B]] | ||
[[Category: Zhao Q]] | [[Category: Zhao, Q]] | ||
[[Category: Cryo-em structure]] | |||
[[Category: Gpcr]] | |||
[[Category: Membrane protein]] | |||
Revision as of 13:14, 7 July 2021
Cryo-EM structure of inactive mGlu2 homodimerCryo-EM structure of inactive mGlu2 homodimer
Structural highlights
Function[GRM2_HUMAN] G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. May mediate suppression of neurotransmission or may be involved in synaptogenesis or synaptic stabilization.[1] [2] [3] [4] 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[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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