9LYC

Cryo-EM structure of GPR3-G protein-dimer complex

Summary for 9LYC

• Entry DOI: 10.2210/pdb9lyc/pdb
• EMDB information: 63523
• Descriptor: G-protein coupled receptor 3, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, ... (5 entities in total)
• Functional Keywords: gpcr, g protein, cryo-em, membrane protein, structural protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 163874.27

Authors

Hua, T.,Liu, Z.J.,Li, X.T.,Chang, H. (deposition date: 2025-02-19, release date: 2025-04-09, Last modification date: 2025-04-16)

Primary citation

Chang, H.,Li, X.,Tu, H.,Wu, L.,Yu, Y.,Liu, J.,Chen, N.,Shen, W.L.,Hua, T.
Structural basis of oligomerization-modulated activation and autoinhibition of orphan receptor GPR3.
Cell Rep, 44:115478-115478, 2025

PubMed Abstract: G protein-coupled receptor 3 (GPR3) is a class A orphan receptor characterized by high constitutive activity in the G signaling pathway. GPR3 has been implicated in Alzheimer's disease and the regulation of thermogenesis in human adipocytes, yet the molecular mechanisms underlying its self-activation and potential endogenous modulators remain unclear. In this study, we present cryo-electron microscopy (cryo-EM) structures of GPR3 in different oligomerization states, both in the absence and presence of G protein. Notably, in addition to the monomeric form of GPR3, our findings reveal a functional GPR3 dimer with an extensive dimer interface-a feature rarely observed in class A GPCRs. Moreover, oligomerization appears to be linked to a unique autoinhibition mechanism involving intracellular loops, which may regulate GPR3 signaling. Collectively, these results provide new insights into the oligomerization-modulated activation of orphan GPCRs, advancing our understanding of their signaling properties.

PubMed: 40158220
DOI: 10.1016/j.celrep.2025.115478

Experimental method

ELECTRON MICROSCOPY (3.06 Å)