Schematic representation of AaFtsH sequence and proposed model for substrate entry.A, bioinformatics tools and available structures of FtsH domains, from E. coli and A. aeolicus, show the presence of a loop-like peptide structure with ∼20 aa between membrane and AAA domains. The N-terminal periplasmic domain (green) is between two transmembrane helices (yellow). The second transmembrane helix is followed by a loop region (gray; see text), which is the link to the AAA+ domain (blue). Connected by the glycine linker (red), the C-terminal protease domain is shown in purple. B, a new model for substrate entry is proposed. The ∼20-aa flexible linker could allow the cytosolic domain of FtsH to tilt in relation to the membrane, creating a 30-Å wide gap that provides access of cytosolic (pink, C) and membrane protein substrates (black, D) to the central pore in a partially folded state.