Exploring the molecular features of protein substrates determining the susceptibility to FtsH-mediated protein degradation

AAA+ proteases are universally conserved molecular machines that utilize ATP hydrolysis to actively unfold substrate proteins and translocate them into a compartmental protease for degradation. This combined activity is central to the removal of misfolded and intrinsically unstable proteins or the proteins that are no longer needed. The FtsH family enzymes are only membrane-integrated AAA+ proteases. In the membranes of bacteria, mitochondria and chloroplasts, FtsH and homologous enzymes play a pivotal role in membrane protein quality control and regulatory circuits degrading both membrane and water-soluble proteins.