FtsH protease-mediated regulation of various cellular functions

Abstract

FtsH, a member of the AAA (ATPases associated with a variety of cellular activities) family of proteins, is an ATP-dependent protease of ∼71 kDa anchored to the inner membrane. It plays crucial roles in a variety of cellular processes. It is responsible for the degradation of both membrane and cytoplasmic substrate proteins. Substrate proteins are unfolded and translocated through the central pore of the ATPase domain into the proteolytic chamber, where the polypeptide chains are processively degraded into short peptides. FtsH is not only involved in the proteolytic elimination of unnecessary proteins, but also in the proteolytic regulation of a number of cellular functions. Its role in proteolytic regulation is achieved by one of two approaches, either the cellular levels of a regulatory protein are controlled by processive degradation of the entire protein, or the activity of a particular substrate protein is modified by processing. In the latter case, protein processing requires the presence of a stable domain within the substrate. Since FtsH does not have a robust unfolding activity, this stable domain is sufficient to abort processive degradation of the protein - resulting in release of a stable protein fragment.