Structural insights into the lipid transfer mechanism of a non-specific lipid transfer protein

The non-specific lipid transfer protein (nsLTP) transfers a variety of lipids between membranes and plays an important role in membrane biogenesis and regulating intra cellular fatty acid pools. However, the mechanism of lipid transfer remained enigmatic. We co-crystallized lipids with nsLTP under a wide range of conditions and determined crystal structures of four intermediate lipid bound states. In addition to the canonical lipid binding site inside the hydrophobic cavity, two different transient lipid binding sites on the surface were discovered. Crystal structures and spectroscopic studies revealed lipid dependent conformation changes indicated that the transiently bound lipid on the protein surface enters inside the cavity via tail-in-mechanism. Molecular dynamics simulation corroborated these data revealing a model for the lipid transfer mechanism.

For full article: https://onlinelibrary.wiley.com/doi/abs/10.1111/tpj.14627