7epf

From Proteopedia

(Difference between revisions)

Revision as of 16:59, 29 November 2023

Crystal structure of mGlu2 bound to NAM597

Structural highlights

7epf is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.7Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FLAV_DESVH Low-potential electron donor to a number of redox enzymes.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 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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gonzalez-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, Lopez-Gimenez JF, Zhou M, Okawa Y, Callado LF, Milligan G, Gingrich JA, Filizola M, Meana JJ, Sealfon SC. Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature. 2008 Mar 6;452(7183):93-7. doi: 10.1038/nature06612. Epub 2008 Feb 24. PMID:18297054 doi:http://dx.doi.org/10.1038/nature06612
↑ Delille HK, Becker JM, Burkhardt S, Bleher B, Terstappen GC, Schmidt M, Meyer AH, Unger L, Marek GJ, Mezler M. Heterocomplex formation of 5-HT2A-mGlu2 and its relevance for cellular signaling cascades. Neuropharmacology. 2012 Jun;62(7):2184-91. doi: 10.1016/j.neuropharm.2012.01.010., Epub 2012 Jan 25. PMID:22300836 doi:http://dx.doi.org/10.1016/j.neuropharm.2012.01.010
↑ Moreno JL, Muguruza C, Umali A, Mortillo S, Holloway T, Pilar-Cuellar F, Mocci G, Seto J, Callado LF, Neve RL, Milligan G, Sealfon SC, Lopez-Gimenez JF, Meana JJ, Benson DL, Gonzalez-Maeso J. Identification of three residues essential for 5-hydroxytryptamine 2A-metabotropic glutamate 2 (5-HT2A.mGlu2) receptor heteromerization and its psychoactive behavioral function. J Biol Chem. 2012 Dec 28;287(53):44301-19. doi: 10.1074/jbc.M112.413161. Epub, 2012 Nov 5. PMID:23129762 doi:http://dx.doi.org/10.1074/jbc.M112.413161
↑ Flor PJ, Lindauer K, Puttner I, Ruegg D, Lukic S, Knopfel T, Kuhn R. Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 2. Eur J Neurosci. 1995 Apr 1;7(4):622-9. PMID:7620613
↑ 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. Structures of human mGlu2 and mGlu7 homo- and heterodimers. Nature. 2021 Jun;594(7864):589-593. doi: 10.1038/s41586-021-03641-w. Epub 2021, Jun 16. PMID:34135509 doi:http://dx.doi.org/10.1038/s41586-021-03641-w

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7epf"

@@ Line 3: / Line 3: @@
 <StructureSection load='7epf' size='340' side='right'caption='[[7epf]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7epf]] 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=7EPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EPF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7epf]] is a 1 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=7EPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EPF FirstGlance]. <br>
-</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=J9U:(8~{R})-4-[2,4-bis(fluoranyl)phenyl]-8-methyl-7-[(2-methylpyrazol-3-yl)methyl]-6,8-dihydro-5~{H}-1,7-naphthyridine-2-carboxamide'>J9U</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</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=J9U:(8~{R})-4-[2,4-bis(fluoranyl)phenyl]-8-methyl-7-[(2-methylpyrazol-3-yl)methyl]-6,8-dihydro-5~{H}-1,7-naphthyridine-2-carboxamide'>J9U</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=7epf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7epf OCA], [https://pdbe.org/7epf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7epf RCSB], [https://www.ebi.ac.uk/pdbsum/7epf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7epf ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/FLAV_DESVH FLAV_DESVH] Low-potential electron donor to a number of redox enzymes.[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 ==
@@ Line 16: / Line 19: @@
 </div>
 <div class="pdbe-citations 7epf" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Metabotropic glutamate receptor 3D structures|Metabotropic glutamate receptor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[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]]

7epf

From Proteopedia

Revision as of 16:59, 29 November 2023

Crystal structure of mGlu2 bound to NAM597

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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