7YFC

Cryo-EM structure of the histamine-bound histamine H4 receptor and Gq complex

Summary for 7YFC

• Entry DOI: 10.2210/pdb7yfc/pdb
• EMDB information: 33785
• Descriptor: Engineered G-alpha-q, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, scFv16, ... (8 entities in total)
• Functional Keywords: gpcr, aminergic receptor, histamine receptor, membrane protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 196304.72

Authors

Im, D.,Iwata, S.,Asada, H. (deposition date: 2022-07-08, release date: 2023-10-25, Last modification date: 2024-11-06)

Primary citation

Im, D.,Kishikawa, J.I.,Shiimura, Y.,Hisano, H.,Ito, A.,Fujita-Fujiharu, Y.,Sugita, Y.,Noda, T.,Kato, T.,Asada, H.,Iwata, S.
Structural insights into the agonists binding and receptor selectivity of human histamine H 4 receptor.
Nat Commun, 14:6538-6538, 2023

PubMed Abstract: Histamine is a biogenic amine that participates in allergic and inflammatory processes by stimulating histamine receptors. The histamine H receptor (HR) is a potential therapeutic target for chronic inflammatory diseases such as asthma and atopic dermatitis. Here, we show the cryo-electron microscopy structures of the HR-G complex bound with an endogenous agonist histamine or the selective agonist imetit bound in the orthosteric binding pocket. The structures demonstrate binding mode of histamine agonists and that the subtype-selective agonist binding causes conformational changes in Phe344, which, in turn, form the "aromatic slot". The results provide insights into the molecular underpinnings of the agonism of HR and subtype selectivity of histamine receptors, and show that the HR structures may be valuable in rational drug design of drugs targeting the HR.

PubMed: 37863901
DOI: 10.1038/s41467-023-42260-z

Experimental method

ELECTRON MICROSCOPY (3 Å)