8jcw

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'''Unreleased structure'''
 
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The entry 8jcw is ON HOLD until Paper Publication
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==Cryo-EM structure of mGlu2-mGlu3 heterodimer in presence of LY341495 and NAM563 (dimerization mode I)==
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<StructureSection load='8jcw' size='340' side='right'caption='[[8jcw]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8jcw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8JCW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JCW FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8jcw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jcw OCA], [https://pdbe.org/8jcw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jcw RCSB], [https://www.ebi.ac.uk/pdbsum/8jcw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jcw ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/FKB1A_HUMAN FKB1A_HUMAN] Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruites SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.<ref>PMID:9233797</ref> <ref>PMID:16720724</ref> [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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Heterodimerization of the metabotropic glutamate receptors (mGlus) has shown importance in the functional modulation of the receptors and offers potential drug targets for treating central nervous system diseases. However, due to a lack of molecular details of the mGlu heterodimers, understanding of the mechanisms underlying mGlu heterodimerization and activation is limited. Here we report twelve cryo-electron microscopy (cryo-EM) structures of the mGlu2-mGlu3 and mGlu2-mGlu4 heterodimers in different conformational states, including inactive, intermediate inactive, intermediate active and fully active conformations. These structures provide a full picture of conformational rearrangement of mGlu2-mGlu3 upon activation. The Venus flytrap domains undergo a sequential conformational change, while the transmembrane domains exhibit a substantial rearrangement from an inactive, symmetric dimer with diverse dimerization patterns to an active, asymmetric dimer in a conserved dimerization mode. Combined with functional data, these structures reveal that stability of the inactive conformations of the subunits and the subunit-G protein interaction pattern are determinants of asymmetric signal transduction of the heterodimers. Furthermore, a novel binding site for two mGlu4 positive allosteric modulators was observed in the asymmetric dimer interfaces of the mGlu2-mGlu4 heterodimer and mGlu4 homodimer, and may serve as a drug recognition site. These findings greatly extend our knowledge about signal transduction of the mGlus.
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Authors:
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Structural insights into dimerization and activation of the mGlu2-mGlu3 and mGlu2-mGlu4 heterodimers.,Wang X, Wang M, Xu T, Feng Y, Shao Q, Han S, Chu X, Xu Y, Lin S, Zhao Q, Wu B Cell Res. 2023 Jun 8. doi: 10.1038/s41422-023-00830-2. PMID:37286794<ref>PMID:37286794</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 8jcw" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Feng Y]]
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[[Category: Han S]]
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[[Category: Lin S]]
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[[Category: Wang M]]
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[[Category: Wang X]]
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[[Category: Wu B]]
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[[Category: Xu T]]
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[[Category: Zhao Q]]

Revision as of 09:41, 21 June 2023

Cryo-EM structure of mGlu2-mGlu3 heterodimer in presence of LY341495 and NAM563 (dimerization mode I)

PDB ID 8jcw

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