Determining structure and function of an ATP-driven membrane bound protease
(together with Marie-Eve Aubin-Tam, TU Delft).
The structure and function of a bacterial ATP driven membrane anchored AAA protease will be elucidated. This protease forms a hexameric ring, and is responsible for the elimination of misfolded membrane proteins. Mutants exhibit growth retardation and reduced protein export. Mitochondrial homologs in humans appear to be related to age-related diseases. These membrane bond proteases perform two functions: 1) they unravel the misfolded protein stuck in the membrane, and 2) the degrade it proteolytically. To pull the substrate into the nanomachinery, force is required. Its measurement is one goal of the work. To elucidate the structure of the AAA protease and its conformational changes is the second goal of the project.