Urea Transporter B (UT-B; SLC14A1); A Target Enabling Package

UT-B is a member of urea transporter family, which consists of two members (UT-A and UT-B). UT-B is primarily a urea channel transporting urea molecules across plasma membrane by concentration gradient. While UT-B is widely expressed, it is particularly important in red blood cells (RBCs). UT-B is associated with improved response to hydroxyurea treatment in sickle cell diseases due to its transport of hydroxyurea into RBCs, and it is the primary antigen for Kidd (Jk) blood group as well as an accessory protein for ABO blood group. UT-B is responsible for urea transport in the vasa recta of kidney, with secondary effect on controlling the urine volume. This makes UT-B a potential target for the development of a new class of diuretics. This TEP presents the structure of UT-B in apo and inhibitor-bound states, determined by crystallography and cryo-electron microscopy, respectively. We have also confirmed the binding of an inhibitor molecule to UT-B in vitro using a biophysical assay. These enable the molecular characterisation of UT-B as an important blood antigen and will also aid further improvement of the inhibitors as a novel therapy for diuretics and potentially neurodegenerative disorders.