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Cartoon representation of the transport cycle depicting the rearrangements of SLC35B1 bundles (teal and orange) to import ATP into the ER in exchange for ADP. A homology model for the occluded (OC) state was constructed using the AlphaFold 2 model 44 of the SLC35B1 homologue from Wuchereria bancrofti (AF-A0A3P7E1A7-F1-v4). AMPPNP and ADP in the occluded state were positioned as in the experimental outward-facing (OF) states. The peripheral TM5 and TM10 helices were omitted for clarity. The insert (asterisk) illustrates that we postulated that ADP initially interacted with phosphate first from the ER luminal side but was then flipped in the binding pocket to the coordination observed by cryo-EM. IF, inward-facing. Graphic in a was created using BioRender ( https://biorender.com ).

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