title: The archaeal proteasome is regulated by a network of AAA ATPases.
abstract: The proteasome is the central machinery for targeted protein degradation in archaea, Actinobacteria, and eukaryotes. In its basic form, it consists of a regulatory ATPase complex and a proteolytic core particle. The interaction between the two is governed by an HbYX motif (where Hb is a hydrophobic residue, Y is tyrosine, and X is any amino acid) at the C terminus of the ATPase subunits, which stimulates gate opening of the proteasomal α-subunits. In archaea, the proteasome-interacting motif is not only found in canonical proteasome-activating nucleotidases of the PAN/ARC/Rpt group, which are absent in major archaeal lineages, but also in proteins of the CDC48/p97/VAT and AMA groups, suggesting a regulatory network of proteasomal ATPases. Indeed, Thermoplasma acidophilum, which lacks PAN, encodes one CDC48 protein that interacts with the 20S proteasome and activates the degradation of model substrates. In contrast, Methanosarcina mazei contains seven AAA proteins, five of which, both PAN proteins, two out of three CDC48 proteins, and the AMA protein, function as proteasomal gatekeepers. The prevalent presence of multiple, distinct proteasomal ATPases in archaea thus results in a network of regulatory ATPases that may widen the substrate spectrum of proteasomal protein degradation.
authors.affiliation: Department of Protein Evolution, Max Planck Institute for Developmental Biology, D-72076 Tübingen, Germany.
authors.forename: Dara
authors.initials: D
authors.lastname: Forouzan
authors.forename: Moritz
authors.initials: M
authors.lastname: Ammelburg
authors.forename: Cedric F
authors.initials: CF
authors.lastname: Hobel
authors.forename: Luisa J
authors.initials: LJ
authors.lastname: Ströh
authors.forename: Nicole
authors.initials: N
authors.lastname: Sessler
authors.forename: Jörg
authors.initials: J
authors.lastname: Martin
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Lupas
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism* / Q000502:physiology; D000595:Amino Acid Sequence; D001105:Archaea / Q000502:physiology*; D019843:Archaeal Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D002853:Chromatography, Liquid / Q000379:methods; D003001:Cloning, Molecular; D019295:Computational Biology / Q000379:methods; D019848:Gene Expression Regulation, Archaeal; D013058:Mass Spectrometry / Q000379:methods; D017020:Methanosarcina / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D010802:Phylogeny; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D013379:Substrate Specificity; D020349:Surface Plasmon Resonance; D013822:Thermoplasma / Q000378:metabolism; D000074405:Valosin Containing Protein
chemical_list: D019843:Archaeal Proteins; D018797:Cell Cycle Proteins; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C420334:PAN enzyme; D000074405:Valosin Containing Protein