Cryo-EM structures of the archaeal PAN-proteasome reveal an around-the-ring ATPase cycle

• DOI: 10.1073/pnas.1817752116
• Publication Date: 2018-12-18T01:15:08Z
• Authors: Parijat Majumder; Till Rudack; Florian Beck; Radostin Danev; Günter Pfeifer; István Nagy; Wolfgang Baumeister
• Keywords: AAA proteins; Protein Degradation

Proteasomes occur in all three domains of life, and are the principal molecular machines for regulated degradation intracellular proteins. They play key roles maintenance protein homeostasis, control vital cellular processes. While eukaryotic 26S proteasome is extensively characterized, its putative evolutionary precursor, archaeal proteasome, remains poorly understood. The primordial consists a 20S proteolytic core particle (CP), an AAA-ATPase module. This minimal complex degrades unassisted by non-ATPase subunits that present regulatory (RP). Using cryo-EM single-particle analysis, we determined structures CP with PAN (proteasome-activating nucleotidase). Five conformational states were identified, elucidating functional cycle PAN, interaction CP. Coexisting nucleotide states, correlated intersubunit signaling features, coordinate rotation PAN-ATPase staircase, allosterically regulate N-domain motions gate opening. These findings reveal structural basis sequential around-the-ring ATPase cycle, which likely conserved AAA-ATPases.