Elucidating the pH gating mechanism of Helicobacter pyloris urea channel UreI

Over 50% of the world population suffer from chronic gastric infection with Helicobacter pyloris which is linked to peptic ulcer disease and stomach cancer. Yet, the efficacy of the common therapy including antibiotics is decreasing. An alternative drug target could be H. pyloris pH gatedinner-membrane urea channel UreI, which is pivotal for the survival of the pathogen in the acidic environment of the human stomach. However, despite in vivo studies and high-resolution structures in the open and closed state, HpUreIs gating mechanism is still elusive. Using yeast complementation assays, we tested (i) homologues urea channels,(ii) point mutations of charged residues also on the cytoplasmic side, and (iii) variants carrying changes at the periplasmic side at the N-and C-terminus as well as in periplasmic loop 1 (PL1). The functionality and pH gating behaviour of these constructs are compared to the wild type protein …