Conformational transition of the lid helix covering the protease active site is essential for the ATP-dependent protease activity of FtsH

When bound to ADP, ATP-dependent protease FtsH subunits adopt either an open or closed conformation. In the open state, the protease catalytic site is located in a narrow space covered by a lid-like helix. This space disappears in the closed form because the lid helix bends at Gly448. Here, we replaced Gly448 with various residues that stabilize helices. Most mutants retained low ATPase activity and bound to the substrate protein, but lost protease activity. However, a mutant proline substitution lost both activities. Our study shows that the conformational transition of the lid helix is essential for the function of FtsH. Structured summary of protein interactions: FtsH and FtsH bind by molecular sieving (View Interaction) (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.