Basal Histamine H₄ Receptor Activation: Agonist Mimicry by the Diphenylalanine Motif.

ABSTRACT: Histamine H₄ receptor (H₄ R) orthologues are G-protein-coupled receptors (GPCRs) that exhibit species-dependent basal activity. In contrast to the basally inactive mouse H₄ R (mH₄ R), human H₄ R (hH₄ R) shows a high degree of basal activity. We have performed long-timescale molecular dynamics simulations and rigidity analyses on wild-type hH₄ R, the experimentally characterized hH₄ R variants S179M, F169V, F169V+S179M, F168A, and on mH₄ R to investigate the molecular nature of the differential basal activity. H₄ R variant-dependent differences between essential motifs of GPCR activation and structural stabilities correlate with experimentally determined basal activities and provide

SUBMITTER: Wifling D 

PROVIDER: S-EPMC7687114 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature