Fig. 3.

Structural changes of ABCB4 during transport cycle. (A) Horizontal slices through the TMDs of available ABCB4 structures, shown from the inside of the cell. TM helices are shown as ribbons and numbered. Bound PC and posaconazole and the side chain of W234 are shown as sticks. The orange arrow shows the side entrance from the inner leaflet of the membrane. (B) Proposed structure-based reaction mechanism. The N- and carboxyl-terminal halves of ABCB4 are colored yellow and blue. The red arch depicts the choline binding site including the side chain of W234. Numbers in yellow circles depict functionally relevant conformational states: States 1, 2, and 2′ represent structures from this study, state 4 is based on PDB: 6s7p (12), and state 3 is based on a putative outward-open conformation (12).