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==Identification, structure and agonist design of an androgen membrane receptor.==
<StructureSection load='9iv1' size='340' side='right'caption='[[9iv1]], [[Resolution|resolution]] 2.98&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9iv1]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9IV1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9IV1 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]] 2.98&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</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=9iv1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9iv1 OCA], [https://pdbe.org/9iv1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9iv1 RCSB], [https://www.ebi.ac.uk/pdbsum/9iv1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9iv1 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AGRD1_HUMAN AGRD1_HUMAN] Orphan receptor. Signals via G(s)-alpha family of G-proteins (PubMed:22025619, PubMed:22575658). Has protumorigenic function especially in glioblastoma (PubMed:27775701).<ref>PMID:22025619</ref> <ref>PMID:22575658</ref> <ref>PMID:27775701</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Androgens, such as 5alpha-dihydrotestosterone (5alpha-DHT), regulate numerous functions by binding to nuclear androgen receptors (ARs) and potential unknown membrane receptors. Here, we report that the androgen 5alpha-DHT activates membrane receptor GPR133 in muscle cells, thereby increasing intracellular cyclic AMP (cAMP) levels and enhancing muscle strength. Further cryoelectron microscopy (cryo-EM) structural analysis of GPR133-Gs in complex with 5alpha-DHT or its derivative methenolone (MET) reveals the structural basis for androgen recognition. Notably, the presence of the "Phi(F/L)(2.64)-F(3.40)-W(6.53)" and the "F(7.42)xxN/D(7.46)" motifs, which recognize the hydrophobic steroid core and polar groups, respectively, are common in adhesion GPCRs (aGPCRs), suggesting that many aGPCRs may recognize different steroid hormones. Finally, we exploited in silico screening methods to identify a small molecule, AP503, which activates GPR133 and separates the beneficial muscle-strengthening effects from side effects mediated by AR. Thus, GPR133 represents an androgen membrane receptor that contributes to normal androgen physiology and has important therapeutic potentials.

Identification, structure, and agonist design of an androgen membrane receptor.,Yang Z, Ping YQ, Wang MW, Zhang C, Zhou SH, Xi YT, Zhu KK, Ding W, Zhang QY, Song ZC, Zhao RJ, He ZL, Wang MX, Qi L, Ullmann C, Ricken A, Schoneberg T, Gan ZJ, Yu X, Xiao P, Yi F, Liebscher I, Sun JP Cell. 2025 Jan 23:S0092-8674(25)00035-2. doi: 10.1016/j.cell.2025.01.006. PMID:39884271<ref>PMID:39884271</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9iv1" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Ping YQ]]
[[Category: Yang Z]]