ATP-competitive LRRK2 inhibitors interfere with monoclonal antibody binding to the kinase domain of LRRK2 under native conditions. A method to directly monitor the active conformation of LRRK2?

► Efficient immunoprecipitation of endogenous LRRK2 by an antibody directed against the LRRK2 N-terminus. ► Immunoprecipitation by an antibody against the kinase domain is impaired by LRRK2 inhibitors. ► The antibody epitope localizes to the aEF/aF loop neighboring the activation segment. ► The antibody may preferentially bind to the active conformation of LRRK2.