Journal article
Lipid-Dependent Activation of the Orphan G Protein-Coupled Receptor, GPR3
Isabella C Russell, Xin Zhang, Fabian Bumbak, Samantha M McNeill, Tracy M Josephs, Michael G Leeming, George Christopoulos, Hariprasad Venugopal, Maria M Flocco, Patrick M Sexton, Denise Wootten, Matthew J Belousoff
Biochemistry | American Chemical Society | Published : 2024
Abstract
The class A orphan G protein-coupled receptor (GPCR), GPR3, has been implicated in a variety of conditions, including Alzheimer’s and premature ovarian failure. GPR3 constitutively couples with Gαs, resulting in the production of cAMP in cells. While tool compounds and several putative endogenous ligands have emerged for the receptor, its endogenous ligand, if it exists, remains a mystery. As novel potential drug targets, the structures of orphan GPCRs have been of increasing interest, revealing distinct modes of activation, including autoactivation, presence of constitutively activating mutations, or via cryptic ligands. Here, we present a cryo-electron microscopy (cryo-EM) structure of the..
View full abstractRelated Projects (2)
Grants
Funding Acknowledgements
This work was supported by resources from the Bio21 Institute Ian Holmes Imaging Centre, the Monash Massive M3 computational infrastructure, and the Monash Ramaciotti Centre for Cryo-Electron Microscopy. We acknowledge the use and assistance of the Bio21 Mass Spectrometry and Proteomics Facility at the University of Melbourne.