title: Mechanisms of molecular transport through the urea channel of Helicobacter pylori.
abstract: Helicobacter pylori survival in acidic environments relies on cytoplasmic hydrolysis of gastric urea into ammonia and carbon dioxide, which buffer the pathogen's periplasm. Urea uptake is greatly enhanced and regulated by HpUreI, a proton-gated inner membrane channel protein essential for gastric survival of H. pylori. The crystal structure of HpUreI describes a static snapshot of the channel with two constriction sites near the center of the bilayer that are too narrow to allow passage of urea or even water. Here we describe the urea transport mechanism at atomic resolution, revealed by unrestrained microsecond equilibrium molecular dynamics simulations of the hexameric channel assembly. Two consecutive constrictions open to allow conduction of urea, which is guided through the channel by interplay between conserved residues that determine proton rejection and solute selectivity. Remarkably, HpUreI conducts water at rates equivalent to aquaporins, which might be essential for efficient transport of urea at small concentration gradients.
authors.affiliation: 1] Center for Biomembrane Systems & Department of Molecular Biology & Biochemistry, University of California, Irvine, California 92697, USA [2].
authors.forename: Reginald
authors.initials: R
authors.lastname: McNulty
authors.forename: Jakob P
authors.initials: JP
authors.lastname: Ulmschneider
authors.forename: Hartmut
authors.initials: H
authors.lastname: Luecke
authors.forename: Martin B
authors.initials: MB
authors.lastname: Ulmschneider
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001692:Biological Transport; D016480:Helicobacter pylori / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D014508:Urea / Q000378:metabolism*; D014867:Water / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; C114527:UreI protein, Helicobacter pylori; D014867:Water; D014508:Urea