Structural insights into ligand recognition and G protein preferences across histamine receptors.

ABSTRACT: Histamine exerts critical physiological roles by activating four receptor subtypes, each exhibiting a specific G protein preference. Among these, the histamine H₄ receptor (H₄R) modulates chemotaxis and interferon production through G_i protein activation, suggesting its therapeutic potential. Despite its physiological significance, the mechanisms underlying H₄R signalling and G protein preference across histamine receptors remain poorly understood. Here, we present the cryo-electron microscopy structure of the H₄R-G_i complex, revealing unique mechanisms of histamine recognition and receptor activation. We further solved the structures of the histamine H₁ receptor (H₁R) bound to the non-canonical G prote

SUBMITTER: Matsuzaki Y 

PROVIDER: S-EPMC12205060 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature