Crystal structure of staphylococcal lukF delineates conformational changes accompanying formation of a transmembrane channel

Staphylococcal LukF, LukS, HγII, and α-hemolysin are self-assembling, channel-forming proteins related in sequence and function. In the α- hemolysin heptamer, the channel-forming β-strands and the amino latch make long excursions from the protomer core. Here we report the crystal structure of the water soluble form of LukF. In the LukF structure the channel-forming region folds into an amphipathic, three-strand β-sheet and the amino latch forms a β-strand extending a central β-sheet. The LukF structure illustrates how a channel-forming toxin masks protein-protein and protein- membrane interfaces prior to cell binding and assembly, and together with the α-hemolysin heptamer structure, they define the end points on the pathway of toxin assembly.