Fig. 3

Positions of amino acids Ser242 (S242) and Ser346 (S346) in the human ABCB4 membrane-spanning domains. (A) General view of the experimental 3D structures of human ABCB4 membrane-spanning domains in the ATP-bound, collapsed (pdb 6S7P¹⁹, , the apo inward-facing (pdb 7NIU²⁰, , the inhibited inward-facing (pdb 7NIW, complex with PC and posaconazole²⁰, and the occluded (pdb 7NIV, complex with PC²⁰ conformations. Amino acids Ser242 (S242) and Ser346 (S346) whose mutations were analyzed in this study are colored green. The three aromatic amino acids (W234, F345, H989) participating in the substrate binding pocket are depicted in orange. DLP stands for 1,2-Dilinoleoyl-Sn-Glycero-3-Phosphocholine. (B) Enlarged view of TM4 (in magenta) and TM6 (in blue) at the level of amino acid S242 in the ATP-bound, collapsed (pdb 6s7p¹⁹, and occluded (pdb 7NIV, complex with PC²⁰ conformations. (C) Contact established between S242 and the headgroup of a POPS molecule in the MD simulation of the apo inward-facing conformation (second replica, also see Table S2) (D) Enlarged view of TM4 (in magenta) and TM6 (in blue) at the level of amino acid S346 in the four conformations depicted in panel A. At right are shown the details of the H-bonds that S346 forms with I342 (red dashed lines). In the red box is shown the tight contact formed between TM4 (A231-A232) and TM6 (G348) in the occluded conformation.