PT  - JOURNAL ARTICLE
AU  - Jessica M. Gullett
AU  - Maxime G. Cuypers
AU  - Christy R. Grace
AU  - Shashank Pant
AU  - Chitra Subramanian
AU  - Emad Tajkhorshid
AU  - Charles O. Rock
AU  - Stephen W. White
TI  - Structural transitions permitting ligand entry and exit in bacterial fatty acid binding proteins
AID  - 10.1101/2021.09.16.460654
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.09.16.460654
4099  - http://biorxiv.org/content/early/2021/09/16/2021.09.16.460654.short
4100  - http://biorxiv.org/content/early/2021/09/16/2021.09.16.460654.full
AB  - Fatty acid (FA) transfer proteins extract FA from membranes and sequester their ligand to facilitate its movement through the cytosol. While detailed views of soluble protein-FA complexes are available, how FA exchange occurs at the membrane has remained unknown. Staphylococcus aureus FakB1 is a prototypical bacterial FA transfer protein that binds palmitate within a narrow, buried tunnel. Here, we determine the conformational change from this closed state to an open state that engages the phospholipid bilayer. Upon membrane binding, a dynamic loop in FakB1 that covers the FA binding site disengages and folds into an amphipathic helix. This helix inserts below the phosphate plane of the bilayer to create a diffusion channel for the FA to exchange between the protein and the membrane. The structure of the bilayer-associated conformation of FakB1 has local similarities with mammalian FA binding proteins and provides a general conceptual framework for how these proteins interact with the membrane to promote lipid transfer.Competing Interest StatementThe authors have declared no competing interest.