Figure 1.

Two proposed mechanisms of lipid transport by lipid transfer proteins (LTPs). (A) Lipid conveyance across the cytoplasm by cytosolic LTP. Cytosolic LTP (e.g., STARD containing proteins 1-7) contains only lipid-transfer domain (LTD) (green) but lacks any membrane binding domain. A ligand-free form of LTP interacts with the donor membrane to acquire a lipid molecule (yellow). This interaction induces a conformational change of LTP and opens its lipid binding pocket. Once the lipid molecule (yellow) has occupied the pocket, the protein conformational change occurs again, leading to a lid closure. The ligand-bound form of LTP is targeted to the acceptor membrane to deliver the lipid. (B) Lipid transport at MCSs by membrane anchored LTP (e.g., ceramide transfer protein, CERT; oxysterol-binding protein, ORP3). LTP anchors with the donor membrane via its membrane binding domain (purple) and exposes its LTD (green) to the cytoplasm. LTD can extract the lipid molecule (yellow) from the donor membrane and deliver it to a closely positioned acceptor membrane.