Figure 5.

Further interpretation of the MRP1 map. (a) Manual tracing of the paths (red cylinders) of cylindrical regions of continuous density in the MRP1 map (blue mesh at 0.9σ, yellow mesh at 1.25σ), using a slab of the high density region viewed from the expected extracellular side of the protein. The location of the fitted P-gp structure within the map is also displayed (purple ribbon trace), as well as local clusters of cylinders that are roughly related by a local twofold symmetry in terms of position (triangular and oval dashed outlines) as well as tilt (curved arrows). On one side of the region (separated by the dashed line) lie cylindrical densities (A–E) that are not matched by the P-gp structure, and may be part of TMD0. A side view of this region is displayed in panel b, with an estimate of the boundaries of the lipid bilayer (yellow dashed lines). Some of the cylindrical densities extend up into the extracellular region at the top (C,D), whilst some (A,B) extend downwards. A sixth cylindrical path (L2) extends down towards a region occupied by the C-terminal NBD of the fitted P-gp structure, whilst a lozenge-shaped region of density (L1, dashed ellipse) extends towards the opposite NBD. Individual fitting of the MetNI NBDs is shown in the relevant sections of the MRP1 map (panels c–e), as viewed from the same orientation as in Fig. 4 (panels c and d), or as viewed from the cytoplasmic side of the protein (panel e). Scale bars = 1 nm, panels b–e are at the same scale. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)