Molecular Determinant Underlying Selective Coupling of Primary G-Protein by Class A GPCRs.

ABSTRACT: G-protein-coupled receptors (GPCRs) transmit downstream signals predominantly via G-protein pathways. However, the conformational basis of selective coupling of primary G-protein remains elusive. Histamine receptors H₂R and H₃R couple with G_s- or G_i-proteins respectively. Here, three cryo-EM structures of H₂R-G_s and H₃R-G_i complexes are presented at a global resolution of 2.6-2.7 Å. These structures reveal the unique binding pose for endogenous histamine in H₃R, wherein the amino group interacts with E206^5.46 of H₃R instead of the conserved D114^3.32 of other aminergic receptors. Furthermore, comparative analysis of the H₂R-G_s and H_3<

SUBMITTER: Shen Q 

PROVIDER: S-EPMC11187927 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature