7mtq
From Proteopedia
(Difference between revisions)
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==CryoEM Structure of Full-Length mGlu2 in Inactive-State Bound to Antagonist LY341495== | ==CryoEM Structure of Full-Length mGlu2 in Inactive-State Bound to Antagonist LY341495== | ||
| - | <StructureSection load='7mtq' size='340' side='right'caption='[[7mtq]]' scene=''> | + | <StructureSection load='7mtq' size='340' side='right'caption='[[7mtq]], [[Resolution|resolution]] 3.65Å' 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=7MTQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MTQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7mtq]] 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=7MTQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MTQ 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=7mtq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mtq OCA], [https://pdbe.org/7mtq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mtq RCSB], [https://www.ebi.ac.uk/pdbsum/7mtq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mtq 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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Z99:2-[(1S,2S)-2-CARBOXYCYCLOPROPYL]-3-(9H-XANTHEN-9-YL)-D-ALANINE'>Z99</scene></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=7mtq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mtq OCA], [https://pdbe.org/7mtq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mtq RCSB], [https://www.ebi.ac.uk/pdbsum/7mtq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mtq 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 == | ||
| + | Family C G-protein-coupled receptors (GPCRs) operate as obligate dimers with extracellular domains that recognize small ligands, leading to G-protein activation on the transmembrane (TM) domains of these receptors by an unknown mechanism(1). Here we show structures of homodimers of the family C metabotropic glutamate receptor 2 (mGlu2) in distinct functional states and in complex with heterotrimeric Gi. Upon activation of the extracellular domain, the two transmembrane domains undergo extensive rearrangement in relative orientation to establish an asymmetric TM6-TM6 interface that promotes conformational changes in the cytoplasmic domain of one protomer. Nucleotide-bound Gi can be observed pre-coupled to inactive mGlu2, but its transition to the nucleotide-free form seems to depend on establishing the active-state TM6-TM6 interface. In contrast to family A and B GPCRs, G-protein coupling does not involve the cytoplasmic opening of TM6 but is facilitated through the coordination of intracellular loops 2 and 3, as well as a critical contribution from the C terminus of the receptor. The findings highlight the synergy of global and local conformational transitions to facilitate a new mode of G-protein activation. | ||
| + | |||
| + | G-protein activation by a metabotropic glutamate receptor.,Seven AB, Barros-Alvarez X, de Lapeyriere M, Papasergi-Scott MM, Robertson MJ, Zhang C, Nwokonko RM, Gao Y, Meyerowitz JG, Rocher JP, Schelshorn D, Kobilka BK, Mathiesen JM, Skiniotis G Nature. 2021 Jun 30. pii: 10.1038/s41586-021-03680-3. doi:, 10.1038/s41586-021-03680-3. PMID:34194039<ref>PMID:34194039</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7mtq" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Barros-Alvarez X]] | + | [[Category: Barros-Alvarez, X]] |
| - | [[Category: Seven | + | [[Category: Seven, A B]] |
| - | [[Category: Skiniotis G]] | + | [[Category: Skiniotis, G]] |
| + | [[Category: Cryoem structure]] | ||
| + | [[Category: Heterotrimeric g protein]] | ||
| + | [[Category: Membrane protein]] | ||
| + | [[Category: Membrane protein-antagonist complex]] | ||
Revision as of 10:15, 14 July 2021
CryoEM Structure of Full-Length mGlu2 in Inactive-State Bound to Antagonist LY341495
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