title: Energetic and molecular water permeation mechanisms of the human red blood cell urea transporter B.
abstract: Urea transporter B (UT-B) is a passive membrane channel that facilitates highly efficient permeation of urea. In red blood cells (RBC), while the major function of UT-B is to transport urea, it is assumed that this protein is able to conduct water. Here, we have revisited this last issue by studying RBCs and ghosts from human variants with defects of aquaporin 1 (AQP1) or UT-B. We found that UT-B's osmotic water unit permeability (pfunit) is similar to that of AQP1. The determination of diffusional permeability coefficient (Pd) allowed the calculation of the Pf/Pd ratio, which is consistent with a single-file water transport. Molecular dynamic simulations of water conduction through human UT-B confirmed the experimental finding. From these results, we propose an atomistic description of water-protein interactions involved in this permeation. Inside the UT-B pore, five water molecules were found to form a single-file and move rapidly along a channel by hydrogen bond exchange involving two critical threonines. We further show that the energy barrier for water located in the central region coincides with a water dipole reorientation, which can be related to the proton exclusion observed experimentally. In conclusion, our results indicate that UT-B should be considered as a new member of the water channel family.
authors.affiliation: Institut National de la Transfusion Sanguine, Paris, France ; Inserm, UMR_S665, Paris, France ; Université Paris Diderot, Sorbonne Paris Cité, Paris, France ; Laboratory of Excellence GR-Ex., Paris, France.
authors.forename: Slim
authors.initials: S
authors.lastname: Azouzi
authors.affiliation: Institut National de la Transfusion Sanguine, Paris, France ; Inserm, UMR_S665, Paris, France ; Université Paris Diderot, Sorbonne Paris Cité, Paris, France ; Laboratory of Excellence GR-Ex., Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Gueroult
authors.affiliation: Institut National de la Transfusion Sanguine, Paris, France ; Inserm, UMR_S665, Paris, France ; Université Paris Diderot, Sorbonne Paris Cité, Paris, France ; Laboratory of Excellence GR-Ex., Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ripoche
authors.affiliation: Institut National de la Transfusion Sanguine, Paris, France ; Inserm, UMR_S665, Paris, France ; Université Paris Diderot, Sorbonne Paris Cité, Paris, France ; Laboratory of Excellence GR-Ex., Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Genetet
authors.affiliation: Institut National de la Transfusion Sanguine, Paris, France ; Inserm, UMR_S665, Paris, France ; Université Paris Diderot, Sorbonne Paris Cité, Paris, France ; Laboratory of Excellence GR-Ex., Paris, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Colin Aronovicz
authors.affiliation: Institut National de la Transfusion Sanguine, Paris, France ; Inserm, UMR_S665, Paris, France ; Université Paris Diderot, Sorbonne Paris Cité, Paris, France ; Laboratory of Excellence GR-Ex., Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Le Van Kim
authors.affiliation: Institut National de la Transfusion Sanguine, Paris, France ; Inserm, UMR_S665, Paris, France ; Université Paris Diderot, Sorbonne Paris Cité, Paris, France ; Laboratory of Excellence GR-Ex., Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Etchebest
authors.affiliation: Institut National de la Transfusion Sanguine, Paris, France ; Inserm, UMR_S665, Paris, France ; Université Paris Diderot, Sorbonne Paris Cité, Paris, France ; Laboratory of Excellence GR-Ex., Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mouro-Chanteloup
mesh_terms: D000595:Amino Acid Sequence; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism; D002417:Cattle; D002463:Cell Membrane Permeability; D004058:Diffusion; D004734:Energy Metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D007700:Kinetics; D026901:Membrane Transport Proteins / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009995:Osmosis; D016062:Porosity; D011522:Protons; D016415:Sequence Alignment; D055672:Static Electricity; D014867:Water / Q000378:metabolism*; D000096982:Urea Transporters
chemical_list: D000641:Ammonia; D051398:Aquaporin 1; D026901:Membrane Transport Proteins; D011522:Protons; D014867:Water; D000096982:Urea Transporters