Are boundary lipids critical for stabilizing membrane protein folds, then what role does the lipid rearrangement of the boundary layer have on functional conformational dynamics? The crystal structure of LspA from P. aeruginosa bound to a competitive inhibitor was recently determined (pdb id 5DIR; Caffrey Laboratory), and an exciting hypothesis about substrate recognition and cleavage was proposed.The movement of the transmembrane helices to accept substrate indicates lipid could play a role in the conformational dynamics. Although not surprising for a membrane-embedded protease, the fundamental implication of the role of lipids is an area not fully understood, and LspA serves as an excellent model to investigate how lipids stabilize structure and facilitate functional dynamics.
–Tracy Caldwell