Length recognition at the N-terminal tail for the initiation of FtsH-mediated proteolysis

FtsH-mediated proteolysis against membrane proteins is processive, and pres umably involves dislocation of the substrate into the cytosol where the enz ymatic domains of FtsH reside. To study how such a mode of proteolysis is i nitiated, we manipulated N-terminal cytosolic tails of three membrane prote ins. YccA, a natural substrate of FtsH was found to require the N-terminal tail of 20 amino acid residues or longer to be degraded by FtsH in vivo. Th ree unrelated sequences of this segment conferred the FtsH sensitivity to Y ccA. An artificially constructed TM9-PhoA protein, derived from SecY, as we ll as the SecE protein, were sensitized to FtsH by addition of extra amino acid sequences to their N-terminal cytosolic tails. Thus, FtsH recognizes a cytosolic region of sufficient length (similar to 20 amino acids) to initi ate the processive proteolysis against membrane proteins. Such a region is typically at the N-terminus and can be diverse in amino acid sequences.