LAUSR

Rhomboid proteases function in hydrated lipid membrane environments that can impact significantly the catalytic activity of the enzyme. How lipids participate in the reaction coordinate of rhomboid proteases is, however, unclear. We address this question by performing all-atom molecular dynamics simulations of the rhomboid protease from Escherichia coli, GlpG. We study GlpG starting from three different protein crystal structures, and explore interactions with lipids by considering five one-component lipid membranes with different lipid headgroups or alkyl chains, and in mixed membranes of phosphatidylethanolamine and phosphatidylgylcerol lipids. Lipid alkyl chains can visit inter-helical regions of the protein close to the gate helix, which can indicate regions of potential interest for substrate binding. Variability in how the protein can interact with lipids closest to the helical gate region suggests that membrane environments may impact proteolysis by participating in the substrate-binding step of the reaction coordinate.Research was supported in part by funding from the Excellence Initiative of the German Federal and State Governments via the Freie Universitat Berlin, and by an allocation of computing time from HLRN, The North-German Supercomputing Center (bec00076).