9UYN

Cryo-EM structure of the G protein-coupled receptor 1 (GPR1) bound to beta-arrestin 1 in ligand-free state

Summary for 9UYN

• Entry DOI: 10.2210/pdb9uyn/pdb
• EMDB information: 64619
• Descriptor: Chemerin-like receptor 2,Vasopressin V2 receptor, Beta-arrestin-1, Nanobody 32, ... (5 entities in total)
• Functional Keywords: g protein-coupled receptor 1, chemerin, beta-arrestin1, signaling protein, membrane protein/immune system, membrane protein-immune system complex
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 129793.94

Authors

Cai, H.,Lin, X.,Zhao, L.,He, M.,Yu, J.,Zhang, B.,Ma, Y.,Xie, C.,Shui, W.,Zhao, Q.,Zhu, Y.,Wu, B. (deposition date: 2025-05-15, release date: 2025-11-19, Last modification date: 2025-12-03)

Primary citation

Cai, H.,Lin, X.,Zhao, L.,He, M.,Yu, J.,Zhang, B.,Ma, Y.,Chang, X.,Tang, Y.,Luo, T.,Jiang, J.,Ma, M.,Song, W.,Ma, L.,Chu, X.,Yi, C.,Chen, K.,Han, S.,Xie, C.,Shui, W.,Zhao, Q.,Zhu, Y.,Wu, B.
Noncanonical agonist-dependent and -independent arrestin recruitment of GPR1.
Science, 390:eadt8794-eadt8794, 2025

PubMed Abstract: G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors have diverse signaling properties with differential preferences for downstream pathways. Certain receptors, such as the chemerin receptor GPR1, undergo arrestin-mediated internalization but weak G protein signaling. However, the mechanisms of this unusual signaling pattern and its physiological relevance are unclear. We report the structures of GPR1 bound to chemerin and β-arrestin 1 or β-arrestin 2 and an agonist-free GPR1-β-arrestin 1 complex. Upon agonist stimulation, the receptor binds the two arrestins in distinct interaction patterns, which may account for their differential cellular responses. Agonist-independent internalization was mediated by an inactive, constitutively phosphorylated GPR1 that accommodates β-arrestin 1 in an unconventional pocket together with a fatty acid, which potentially provides a basis for GPR1 modulating lipid accumulation in lipid-overloaded adipocytes.

PubMed: 41264711
DOI: 10.1126/science.adt8794

Experimental method

ELECTRON MICROSCOPY (2.9 Å)