title: Distinct quaternary structures of the AAA+ Lon protease control substrate degradation.
abstract: Lon is an ATPase associated with cellular activities (AAA+) protease that controls cell division in response to stress and also degrades misfolded and damaged proteins. Subunits of Lon are known to assemble into ring-shaped homohexamers that enclose an internal degradation chamber. Here, we demonstrate that hexamers of Escherichia coli Lon also interact to form a dodecamer at physiological protein concentrations. Electron microscopy of this dodecamer reveals a prolate structure with the protease chambers at the distal ends and a matrix of N domains forming an equatorial hexamer-hexamer interface, with portals of ∼45 Å providing access to the enzyme lumen. Compared with hexamers, Lon dodecamers are much less active in degrading large substrates but equally active in degrading small substrates. Our results support a unique gating mechanism that allows the repertoire of Lon substrates to be tuned by its assembly state.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Ellen F
authors.initials: EF
authors.lastname: Vieux
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Wohlever
authors.forename: James Z
authors.initials: JZ
authors.lastname: Chen
authors.forename: Robert T
authors.initials: RT
authors.lastname: Sauer
authors.forename: Tania A
authors.initials: TA
authors.lastname: Baker
mesh_terms: D015153:Blotting, Western; D002850:Chromatography, Gel; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007834:Lasers; D008854:Microscopy, Electron; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism; D020125:Mutation, Missense / Q000235:genetics; D049070:Protease La / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D059748:Proteolysis; D012542:Scattering, Radiation; D014461:Ultracentrifugation
chemical_list: D029968:Escherichia coli Proteins; D009097:Multienzyme Complexes; C483567:Lon protein, E coli; D049070:Protease La
keywords: ATP-dependent protease; EM structure; IbpB; regulated proteolysis; substrate gating