Proteasomal AAA-ATPases: Structure and function

Shoshana Bar-Nun*, Michael H. Glickman

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


The 26S proteasome is a chambered protease in which the majority of selective cellular protein degradation takes place. Throughout evolution, access of protein substrates to chambered proteases is restricted and depends on AAA-ATPases. Mechanical force generated through cycles of ATP binding and hydrolysis is used to unfold substrates, open the gated proteolytic chamber and translocate the substrate into the active proteases within the cavity. Six distinct AAA-ATPases (Rpt1-6) at the ring base of the 19S regulatory particle of the proteasome are responsible for these three functions while interacting with the 20S catalytic chamber. Although high resolution structures of the eukaryotic 26S proteasome are not yet available, exciting recent studies shed light on the assembly of the hetero-hexameric Rpt ring and its consequent spatial arrangement, on the role of Rpt C-termini in opening the 20S 'gate', and on the contribution of each individual Rpt subunit to various cellular processes. These studies are illuminated by paradigms generated through studying PAN, the simpler homo-hexameric AAA-ATPase of the archaeal proteasome. The similarities between PAN and Rpts highlight the evolutionary conserved role of AAA-ATPase in protein degradation, whereas unique properties of divergent Rpts reflect the increased complexity and tighter regulation attributed to the eukaryotic proteasome. This article is part of a Special Issue entitled: AAA ATPases: structure and function.

Original languageEnglish
Pages (from-to)67-82
Number of pages16
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Issue number1
StatePublished - Jan 2012


FundersFunder number
Israeli Ministry of Justice
Bloom's Syndrome Foundation
United States-Israel Binational Science Foundation
Israel Science Foundation
Ministry of Health, State of Israel


    • 19S regulatory particle
    • AAA-ATPase
    • PAN
    • Proteasome


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