Schematic illustration of the activity and mechanisms of mitochondrial ATPase-associated with diverse activities (AAA+) proteases as inferred from structural studies.
i-AAA (IMS-facing AAA protease): yeast YME1 (PDB: 6AZ0) [27] homologous to plant FTSH4/11 proteases; m-AAA (IMS-facing AAA protease): human AFG3L2 (PDB: 6NYY) [26] homologous to plant FTSH3/10 proteases; LON (long filamentous phenotype protease): Yersinia pestis Lon (PDB: 6ON2) [25] homologous to plant LON1; CLPXP (caseinolytic protease system): Neisseria meningitidis CLPXP (PDB: 6VFX) [86] homologous to plant CLPXP protease. For each AAA+ proteases, domains are coloured and indicated in linear diagram, with specific features, motifs, and catalytic residues highlighted. Generally, all AAA+ protease sequences contain cleavable targeting peptide (TP) and compose of ATPase that has Walker A and B (WA/WB) nucleotide binding motifs and proteolytic domain. Membrane-embedded i-AAA and m-AAA contain transmembrane domain (TM) and HEXGH zinc-binding motif within the catalytic site. On the other hand, LON and CLP proteases contain SK dyad and SDH triad as catalytic residues, respectively. Substrate is recognised by ATPase domain and unfolded as the multimeric structure is rearranged upon ATP binding and hydrolysis. The unfolded polypeptide is then translocated into the proteolytic chamber within protease domain for degradation into peptide fragments.