View source for 8smv


==GPR161 Gs heterotrimer==
<StructureSection load='8smv' size='340' side='right'caption='[[8smv]], [[Resolution|resolution]] 2.74&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8smv]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SMV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SMV 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]] 2.74&#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></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=8smv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8smv OCA], [https://pdbe.org/8smv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8smv RCSB], [https://www.ebi.ac.uk/pdbsum/8smv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8smv ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The orphan G protein-coupled receptor (GPCR) GPR161 plays a central role in development by suppressing Hedgehog signaling. The fundamental basis of how GPR161 is activated remains unclear. Here, we determined a cryogenic-electron microscopy structure of active human GPR161 bound to heterotrimeric G(s). This structure revealed an extracellular loop 2 that occupies the canonical GPCR orthosteric ligand pocket. Furthermore, a sterol that binds adjacent to transmembrane helices 6 and 7 stabilizes a GPR161 conformation required for G(s) coupling. Mutations that prevent sterol binding to GPR161 suppress G(s)-mediated signaling. These mutants retain the ability to suppress GLI2 transcription factor accumulation in primary cilia, a key function of ciliary GPR161. By contrast, a protein kinase A-binding site in the GPR161 C terminus is critical in suppressing GLI2 ciliary accumulation. Our work highlights how structural features of GPR161 interface with the Hedgehog pathway and sets a foundation to understand the role of GPR161 function in other signaling pathways.

GPR161 structure uncovers the redundant role of sterol-regulated ciliary cAMP signaling in the Hedgehog pathway.,Hoppe N, Harrison S, Hwang SH, Chen Z, Karelina M, Deshpande I, Suomivuori CM, Palicharla VR, Berry SP, Tschaikner P, Regele D, Covey DF, Stefan E, Marks DS, Reiter JF, Dror RO, Evers AS, Mukhopadhyay S, Manglik A Nat Struct Mol Biol. 2024 Apr;31(4):667-677. doi: 10.1038/s41594-024-01223-8. , Epub 2024 Feb 7. PMID:38326651<ref>PMID:38326651</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8smv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Harrison S]]
[[Category: Hoppe N]]
[[Category: Manglik A]]