2.A.40.1.1
Uracil permease, UraA. The crystal structure of UraA with bound uracil at 2.8 Å resolution is available (PDB: 3QE7) (Lu et al., 2011). UraA has a novel structural fold, with 14 TMSs divided into two inverted repeats. A pair of antiparallel β-strands is located between TMS3 and TMS10 and has an important role in structural organization and substrate recognition. The structure is spatially arranged into a core domain and a gate domain. Uracil, located at the interface between the two domains, is coordinated mainly by residues from the core domain. Structural analysis suggests that alternating access of the substrate may be achieved through conformational changes of the gate domain.  Multiscale molecular dynamics simulations of the UraA symporter in phospholipid bilayers revealed a closed state with 3 high affinity binding sites for cardolipin (Kalli et al. 2015).The crystal structure of UraA bound to uracil in an occluded state at 2.5 A resolution (Yu et al. 2017). UraA shows substantial motions between the core domain and the gate domain as well as intra-domain rearrangements of the gate domain. The occluded UraA forms a dimer wherein the gate domains are sandwiched by two core domains. Dimer formation is necessary for transport activity (Yu et al. 2017).