title: Mechanistic insights into bacterial AAA+ proteases and protein-remodelling machines.
abstract: To maintain protein homeostasis, AAA+ proteolytic machines degrade damaged and unneeded proteins in bacteria, archaea and eukaryotes. This process involves the ATP-dependent unfolding of a target protein and its subsequent translocation into a self-compartmentalized proteolytic chamber. Related AAA+ enzymes also disaggregate and remodel proteins. Recent structural and biochemical studies, in combination with direct visualization of unfolding and translocation in single-molecule experiments, have illuminated the molecular mechanisms behind these processes and suggest how remodelling of macromolecular complexes by AAA+ enzymes could occur without global denaturation. In this Review, we discuss the structural and mechanistic features of AAA+ proteases and remodelling machines, focusing on the bacterial ClpXP and ClpX as paradigms. We also consider the potential of these enzymes as antibacterial targets and outline future challenges for the field.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Adrian O
authors.initials: AO
authors.lastname: Olivares
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Tania A
authors.initials: TA
authors.lastname: Baker
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Sauer
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D001419:Bacteria / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D049071:Endopeptidase Clp / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D046911:Macromolecular Substances / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D017510:Protein Folding; D059748:Proteolysis
chemical_list: D046911:Macromolecular Substances; D000255:Adenosine Triphosphate; D049071:Endopeptidase Clp