The Archaeal Proteasome Is Regulated by a Network of AAA ATPases

• Published in: The Journal of biological chemistry Vol. 287; no. 46; pp. 39254 - 39262
• Main Authors: Forouzan, Dara, Ammelburg, Moritz, Hobel, Cedric F., Ströh, Luisa J., Sessler, Nicole, Martin, Jörg, Lupas, Andrei N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.11.2012; American Society for Biochemistry and Molecular Biology
• Subjects: Adenosine Triphosphatases - metabolism; Adenosine Triphosphatases - physiology; Amino Acid Sequence; Archaea; Archaea - physiology; Archaeal Proteins - metabolism; ATP-dependent Protease; ATPases; Cell Cycle Proteins - metabolism; Cell Cycle Proteins - physiology; Chromatography, Liquid - methods; Cloning, Molecular; Computational Biology - methods; Gene Expression Regulation, Archaeal; Mass Spectrometry - methods; Methanosarcina - metabolism; Models, Biological; Molecular Sequence Data; Phylogeny; Proteasome; Proteasome Endopeptidase Complex - metabolism; Protein Degradation; Protein Synthesis and Degradation; Substrate Specificity; Surface Plasmon Resonance; Thermoplasma - metabolism; Valosin Containing Protein; ATPases; Protein Degradation; Archaea; ATP-dependent Protease; Proteasome
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M112.386458

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. Background: The AAA ATPases of the PAN/Rpt1–6 group regulate access of substrates to the 20S proteasome. Results: Two groups of AAA proteins, CDC48 and AMA, function as novel proteasomal ATPases in archaea. Conclusion: This network of regulatory ATPases increases the capacity of proteasomal protein degradation in archaea. Significance: Diversification at the level of the regulatory ATPase provides a contrast to the fully differentiated 26S proteasome of eukaryotes.