The overall objective of PP03 is to provide a detailed mechanistic understanding of molecular processes underlying lipid hydrolysis by biochemical and biophysical characterization of lipases and their regulators. By combining integrated structural biology approaches to corroborate the protein-protein interfaces, PP03 proposes a first 3D-model of a complex comprising ATGL together with its co-activator ABHD5/CGI-58 and its inhibitor G0S2. In addition, PP03 will continue the approach toward the 3D structure of ATGL by cryo-EM and use protein X-ray crystallography to study the mouse Ces2 family members and human CES2. PP03 should establish a clear structure-function correlation, which eventually may lead to the identification of the mouse ortholog(s) of CES2.
