9LRE
Cryo-EM structure of the histamine H4 receptor-Gi protein complex (Overall)
Summary for 9LRE
| Entry DOI | 10.2210/pdb9lre/pdb |
| EMDB information | 63327 |
| Descriptor | Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, scFv16, ... (7 entities in total) |
| Functional Keywords | gpcr, class a gpcr, histamine, g protein, complex, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 192334.94 |
| Authors | Matsuzaki, Y.,Sano, F.K.,Oshima, H.S.,Akasaka, H.,Kobayashi, K.,Tanaka, T.,Itoh, Y.,Shihoya, W.,Kise, Y.,Kusakizako, T.,Nureki, O. (deposition date: 2025-01-30, release date: 2025-06-11, Last modification date: 2025-07-23) |
| Primary citation | Matsuzaki, Y.,Sano, F.K.,Oshima, H.S.,Akasaka, H.,Kobayashi, K.,Tanaka, T.,Itoh, Y.,Shihoya, W.,Kise, Y.,Kusakizako, T.,Inoue, A.,Nureki, O. Structural insights into ligand recognition and G protein preferences across histamine receptors. Commun Biol, 8:957-957, 2025 Cited by 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 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. PubMed: 40579541DOI: 10.1038/s42003-025-08363-7 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.84 Å) |
Structure validation
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