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| Title | Structural insights into ligand recognition and G protein preferences across histamine receptors. |
|---|---|
| Journal, issue, pages | Commun Biol, Vol. 8, Issue 1, Page 957, Year 2025 |
| Publish date | Jun 27, 2025 |
Authors | Yuma Matsuzaki / Fumiya K Sano / Hidetaka S Oshima / Hiroaki Akasaka / Kazuhiro Kobayashi / Tatsuki Tanaka / Yuzuru Itoh / Wataru Shihoya / Yoshiaki Kise / Tsukasa Kusakizako / Asuka Inoue / Osamu Nureki / ![]() |
| PubMed Abstract | Histamine exerts critical physiological roles by activating four receptor subtypes, each exhibiting a specific G protein preference. Among these, the histamine H receptor (HR) modulates chemotaxis ...Histamine exerts critical physiological roles by activating four receptor subtypes, each exhibiting a specific G protein preference. Among these, the histamine H receptor (HR) modulates chemotaxis and interferon production through G protein activation, suggesting its therapeutic potential. Despite its physiological significance, the mechanisms underlying HR signalling and G protein preference across histamine receptors remain poorly understood. Here, we present the cryo-electron microscopy structure of the HR-G complex, revealing unique mechanisms of histamine recognition and receptor activation. We further solved the structures of the histamine H receptor (HR) bound to the non-canonical G proteins G and G. Through a combination of functional and computational analyses, we identified the intracellular loop 2 as a critical determinant of G protein preference in HR and HR. Collectively, our comprehensive study revealed the structural basis for distinct mechanisms of ligand recognition and receptor activation, offering a profound insight into G protein preference across receptor subtypes. |
External links | Commun Biol / PubMed:40579541 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.77 - 3.23 Å |
| Structure data | EMDB-63324, PDB-9lrb: EMDB-63325, PDB-9lrc: EMDB-63326, PDB-9lrd: EMDB-63327, PDB-9lre: |
| Chemicals | ![]() ChemComp-HSM: ![]() ChemComp-HOH: |
| Source |
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Keywords | MEMBRANE PROTEIN / GPCR / Class A GPCR / Histamine / G protein / Complex / Receptor |
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homo sapiens (human)
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