Fig. 4: Models of R region interactions and other ABCC dimer structures.

a Schematic diagrams of the NBD1/R region interactions in the fully phosphorylated Ycf1p monomer (i), the non-phosphorylated Ycf1p monomer (ii), and the partly phosphorylated Ycf1p dimer (iii). Possible locations for unobserved portions of the R region are shown by a diffuse red density to denote its multiple possible interactions, with the most likely locations of the R region in dark red and the less likely locations in light red. The fully phosphorylated R region likely binds the peripheral face of NBD1, allowing for binding (i). ATP is shown with the adenine base and ribose in blue and the phosphates depicted as red circles. The non-phosphorylated R region can bind in the substrate binding cavity⁷⁴ and also contact the ATP binding site of NBD1³⁵ (ii), preventing nucleotide binding. The partly phosphorylated R region in the Ycf1p dimer can interact with the ATP binding site or with the peripheral side of NBD1 (iii). ATP binds when the R regions binds the peripheral side of NBD1. b Schematic diagram of the cleaved Ycf1p dimer (top) and the proposed MRP1 dimer (bottom). Two orientations are shown for each protein. The Ycf1p dimer is viewed from the lumen (top left) and from within the membrane (top right). Similarly, the MRP1 dimer is shown from the extracellular side of the plasma membrane (bottom left) and from within the membrane (bottom right). Transmembrane helices of the cleaved Ycf1p dimer cryo-EM structure and the MRP1 dimer model are shown as cylinders. Transmembrane helices in TMD0 are coloured in orange for Ycf1p, as in Fig. 1a, and in coral for MRP1. As in Fig. 1a, transmembrane helices in TMD1 and TMD2 are in blue and green, respectively, for both proteins. Transmembrane helices in one protomer are labeled with “ ‘ ” to distinguish them from those in the opposite protomer. While the structure of the ABC core is similar in Ycf1p and MRP1, the orientation of TMD0 helices differ slightly between the two proteins, leading to different inter-protomer TMD0 contacts between the Ycf1p and MRP1 dimers.