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| Title | Cryo-EM structure of the bicarbonate receptor GPR30. |
|---|---|
| Journal, issue, pages | Elife, Vol. 13, Year 2026 |
| Publish date | Aug 14, 2026 |
 Authors | Shota Kaneda / Airi Jo-Watanabe / Hiroaki Akasaka / Hidetaka S Oshima / Takehiko Yokomizo / Wataru Shihoya / Osamu Nureki /  |
| 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 ...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. |
 External links | Elife / PubMed:42599157 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.99 - 3.18 Å |
| Structure data |  EMDB-66629: Human GPR30 -Gq complex consensus map  EMDB-66630: Human GPR30 -Gq complex G-protein focused  EMDB-66631: Human GPR30 -Gq complex receptor focused EMDB-66632, PDB-9x74: |
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 Keywords | MEMBRANE PROTEIN / Receptor / GPCR / Complex |
homo sapiens (human)
rattus norvegicus (Norway rat)
mus musculus (house mouse)
bos taurus (domestic cattle)