View source for 9vos


==Cryo-EM Structure of GPR158 in Complex with RGS7-Gbeta5 and Nanobody Nb20==
<StructureSection load='9vos' size='340' side='right'caption='[[9vos]], [[Resolution|resolution]] 4.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9vos]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Lama_glama Lama glama] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9VOS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9VOS FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.3&#8491;</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=PEE:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>PEE</scene>, <scene name='pdbligand=PII:2-[(HYDROXY{[(2R,3R,5S,6R)-2,3,4,5,6-PENTAHYDROXYCYCLOHEXYL]OXY}PHOSPHORYL)OXY]-1-[(PALMITOYLOXY)METHYL]ETHYL+HEPTADECANOATE'>PII</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=9vos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9vos OCA], [https://pdbe.org/9vos PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9vos RCSB], [https://www.ebi.ac.uk/pdbsum/9vos PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9vos ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MGLYR_HUMAN MGLYR_HUMAN] Metabotropic receptor for glycine that controls synapse formation and function in the brain (PubMed:36996198). Acts as an atypical G-protein coupled receptor that recruits and regulates the RGS7-GNB5 complex instead of activating G proteins (PubMed:31189666, PubMed:36996198). In absence of glycine ligand, promotes the GTPase activator activity of RGS7, increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form (PubMed:36996198). Glycine-binding changes the conformation of the intracellular surface, inhibiting the GTPase activator activity of the RGS7-GNB5 complex, promoting G protein alpha subunits into their active GTP-bound form and regulating cAMP levels (PubMed:36996198). Also able to bind taurine, a compound closely related to glycine, but with a two-fold lower affinity (PubMed:36996198). Glycine receptor-dependent regulation of cAMP controls key ion channels, kinases and neurotrophic factors involved in neuronal excitability and synaptic transmission (PubMed:36996198). Plays a pivotal role in regulating mood and cognition via its ability to regulate neuronal excitability in L2/L3 pyramidal neurons of the prefrontal cortex (By similarity). Also involved in spatial learning by regulating hippocampal CA1 neuronal excitability (By similarity). Acts as a synaptic organizer in the hippocampus, required for proper mossy fiber-CA3 neurocircuitry establishment, structure and function: induces presynaptic differentiation in contacting axons via its interaction with GPC4 (By similarity). In addition to glycine, may also act as a receptor for osteocalcin (BGLAP) hormone: osteocalcin-binding initiates a signaling response that prevents neuronal apoptosis in the hippocampus and regulates the synthesis of neurotransmitters (By similarity).[UniProtKB:Q8C419]<ref>PMID:31189666</ref> <ref>PMID:36996198</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Development of therapies for neuropsychiatric conditions is one of the greatest challenges of modern medicine. Common limitations of traditional small molecule drugs include poor efficacy, off-target side effects and difficult druggability of many targets. In this study, we report a different approach deploying small engineered single domain antibodies, known as nanobodies, for the treatment of depression, a prevalent neuropsychiatric condition. We develop highly selective nanobodies for a recently discovered glycine receptor mGlyR crucially linked to pathophysiology of depression. Using a mouse model of stress-induced depression, we show that non-invasive intranasal delivery of nanobody produces rapid and lasting anti-depressant effect. We solve an atomic structure of mGlyR bound to nanobody and use a variety of cell-based approaches to reveal the mechanism of mGlyR modulation and its impact on neural circuitry. These findings support development of biologics for the treatment of intractable brain disorders.

Targeting mGlyR with nanobodies for depression.,Laboute T, Zucca S, Sial OK, Sharma M, Brunori G, Singh S, Nageswar KV, Peng H, Rader C, Becker JA, Le Merrer J, Singh AK, Martemyanov KA Nat Commun. 2026 Jan 26;17(1):831. doi: 10.1038/s41467-026-68339-x. PMID:41588006<ref>PMID:41588006</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9vos" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Brunori G]]
[[Category: Laboute T]]
[[Category: Martemyanov K]]
[[Category: Sharma M]]
[[Category: Sial M]]
[[Category: Singh A]]
[[Category: Singh S]]
[[Category: Zucca S]]