Molecular Dynamics Simulations of the Bacterial UraA H+-Uracil Symporter in Lipid Bilayers Reveal a Closed State and a Selective Interaction with Cardiolipin
A. Occupancy plots showing the probability of occurrence of cardiolipin (CL; green) and of the POPG (red) lipids around UraA. The occupancy was calculated as the average over all repeat coarse-grained simulations of the wild type UraA (UraA-CG in Table 1). Three different views are shown: a side view (left) showing the three CL binding sites, a cytosolic view facing the inner leaflet (middle) showing CL sites 1 and 2, and an extracellular view facing the outer leaflet of the bilayer (right) showing CL site 3. The distribution of all lipids separately is shown in S8 Fig. B. Normalized average number of contacts (using a cut-off distance of 7 Å for POPE and POPG and 8 Å for CL molecules) between the UraA and the head groups of POPG and CL lipids in the bilayer (across all repeats of the extended UraA-CG simulations; see Table 1). For the normalization, the number of contacts of a residue with a lipid type was divided by the number of lipids, the number of frames and the ratio of cutoff volumes. C. The number of contacts from one of the CG-MD simulations was mapped on the UraA crystal structure. Blue indicates a low number, white indicates a medium number and red a large number of contacts.