9X74

Human GPR30 -Gq complex

Summary for 9X74

• Entry DOI: 10.2210/pdb9x74/pdb
• EMDB information: 66632
• Descriptor: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, Guanine nucleotide-binding protein G(i) subunit alpha-2,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, ... (5 entities in total)
• Functional Keywords: receptor, gpcr, complex, membrane protein
• Biological source: Rattus norvegicus (Norway rat); More
• Total number of polymer chains: 5
• Total formula weight: 199109.44

Authors

Kaneda, S.,Oshima, H.S.,Akasaka, H.,Shihoya, W.,Nureki, O. (deposition date: 2025-10-16, release date: 2026-08-26)

Primary citation

Kaneda, S.,Jo-Watanabe, A.,Akasaka, H.,Oshima, H.S.,Yokomizo, T.,Shihoya, W.,Nureki, O.
Cryo-EM structure of the bicarbonate receptor GPR30.
Elife, 13:-, 2026

PubMed Abstract: G-protein-coupled receptor 30 (GPR30) is a bicarbonate receptor that plays a vital role in cellular responses to extracellular pH and ion homeostasis. Despite its significance, the mechanisms by which GPR30 interacts with bicarbonate ions remain elusive. There is no consensus on a drug that targets GPR30, and difficulties in pharmacological analyses have limited biological and drug discovery research on GPR30. Here, we present the cryo-electron microscopy structure of human GPR30 in the presence of bicarbonate ions at 3.15 Å resolution. Our structure reveals unique extracellular pockets and critical residues for bicarbonate binding and activation. Functional assays demonstrate that mutations in these residues impair bicarbonate-induced GPR30 activation, underscoring their importance in receptor function. This study also provides insights into G-protein coupling, highlighting the structural divergence between GPR30 and other G-protein-coupled receptors (GPCRs). Our findings not only advance the understanding of the role of GPR30 in pH homeostasis but also pave the way for the development of high-affinity drugs targeting GPR30 for therapeutic interventions in diseases associated with acid-base imbalance.

PubMed: 42599157
DOI: 10.7554/eLife.99874

Experimental method

ELECTRON MICROSCOPY (3.15 Å)