Fig. 6: Mechanism of carrier-like nonvesicular lipid transport at MCSs.
From: Structural basis for lipid transport at membrane contact sites by the IST2–OSH6 complex
a, Transport mechanism of the IST2–OSH6 system. Center, general organization of the complex consisting of the transmembrane domain of IST2 located in the ER that is tethered to the PM through a lipid-binding region attached to the C terminus of a flexible linker, which contains a binding site for the LTP OSH6 in its center. Left, close-up view of the transport cycle illustrating the shuttling of OSH6 between membranes to mediate the exchange of the lipids PS and PtdIns4P with the IST2 linker acting as an entropic spring. Right, function of the membrane-inserted part to distort the membrane and mediate lipid scrambling between both leaflets to facilitate lipid exchange. b, Analogous processes in higher eukaryotes mediated by the mammalian homologs ORP5 and ORP8. In both cases, the interaction with a lipid scramblase is still hypothetical.
