Fig. 7
From: Direct protein-lipid interactions shape the conformational landscape of secondary transporters

A lipid-mediated mechanism of transport. Model of secondary transport based on the interaction between charge-relay networks of XylE and PE phospholipid (i) Substrate (orange) binds from the extracellular side and stabilizes the OF conformation. (ii) Proton binding triggers closure of the extracellular side. (iii) The fully loaded transporter transitions towards an occluded conformational intermediate. Proton translocates through the transporter to the conserved charge-relay networks (pink) on the intracellular side (iv) Disruption of the charge networks opens the intracellular side. Spontaneous deprotonation upon exposure to the slightly basic cytosol leads to intracellular proton release. (v) Direct interactions between PE and the transporter stabilize the inward-facing conformation, thus facilitating substrate release and completing the transport cycle. Reformation of the cytoplasmic charge-relay networks leads to the subsequent conformational switch. (vi) is equivalent to (i)