Proteasomes and protein conjugation across domains of life

Maupin-Furlow, Julie A.

doi:10.1038/nrmicro2696

Cited by 100 publications

(96 citation statements)

References 120 publications

(195 reference statements)

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“…Each α and β ring consists of 7 subunits which are arranged in α 7 β 7 β 7 α 7 symmetry in the 20S complex. Adapted from (Ciechanover, 2005;Maupin-Furlow, 2012). …”

Section: Figure 11: the Ubiquitin-proteasome System (Ups)mentioning

confidence: 99%

“…The proteasome is a large, self-compartmentalized nanomachine that harbors different proteolytic subunits and is evolutionary conserved across the three domains of life (Baumeister et al, 1998;Maupin-Furlow, 2012). The self-assembly of these proteolytic subunits to form a functionally active proteasome enables the cells to localize them to different cellular locations in the cytosol or in the nucleus, depending on the need.…”

Section: Figure 11: the Ubiquitin-proteasome System (Ups)mentioning

confidence: 99%

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Firefly luciferase mutants as sensors of proteome stress

et al. 2011

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“…Each α and β ring consists of 7 subunits which are arranged in α 7 β 7 β 7 α 7 symmetry in the 20S complex. Adapted from (Ciechanover, 2005;Maupin-Furlow, 2012). …”

Section: Figure 11: the Ubiquitin-proteasome System (Ups)mentioning

confidence: 99%

Section: Figure 11: the Ubiquitin-proteasome System (Ups)mentioning

confidence: 99%

Firefly luciferase mutants as sensors of proteome stress

et al. 2011

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“…For example, homohexamers of Mpa/Arc in actinobacteria and PAN in archaea serve as proteasomal motors, whereas a heterohexameric Rpt 1-6 ring in the 19S particle is the motor of the eukaryotic 26S proteasome (2,5). Characteristic of type-I AAA+ enzymes, Mpa/Arc, PAN, and Rpt 1-6 subunits contain a single AAA+ module for ATP binding and hydrolysis (6).…”

mentioning

confidence: 99%

“…It was proposed that as ATP hydrolysis progresses in the PAN and Rpt 1-6 rings, wobbling motions arise because the HbYX tails of newly ATP-bound subunits interact with binding pockets in the 20S α-subunit, whereas HbYX motifs in posthydrolytic subunits assume a nonbinding conformation (14). However, recent EM studies have shown that the rings of Rpt [1][2][3][4][5][6] and 20S shift into more symmetric and coaxially aligned positions upon substrate engagement, questioning the functional importance of dynamic wobbling (15).…”

mentioning

confidence: 99%

Architecture and assembly of the archaeal Cdc48⋅20S proteasome

Barthelme¹,

Chen²,

Grabenstatter

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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ATP-dependent proteases maintain protein quality control and regulate diverse intracellular functions. Proteasomes are primarily responsible for these tasks in the archaeal and eukaryotic domains of life. Even the simplest of these proteases function as large complexes, consisting of the 20S peptidase, a barrel-like structure composed of four heptameric rings, and one or two AAA+ (ATPase associated with a variety of cellular activities) ring hexamers, which use cycles of ATP binding and hydrolysis to unfold and translocate substrates into the 20S proteolytic chamber. Understanding how the AAA+ and 20S components of these enzymes interact and collaborate to execute protein degradation is important, but the highly dynamic nature of prokaryotic proteasomes has hampered structural characterization. Here, we use electron microscopy to determine the architecture of an archaeal Cdc48·20S proteasome, which we stabilized by site-specific cross-linking. This complex displays coaxial alignment of Cdc48 and 20S and is enzymatically active, demonstrating that AAA+ unfoldase wobbling with respect to 20S is not required for function. In the complex, the N-terminal domain of Cdc48, which regulates ATP hydrolysis and degradation, packs against the D1 ring of Cdc48 in a coplanar fashion, constraining mechanisms by which the N-terminal domain alters 20S affinity and degradation activity.AAA+ protease | dynamic wobbling model | p97/VCP P roteasomes are large macromolecular complexes that degrade misfolded or damaged proteins to maintain cellular homeostasis and quality control in all domains of life. In addition, selective proteasomal turnover of regulatory proteins is often a critical element of signaling cascades that allow cells to respond to changing conditions and environmental stress (1, 2). Proteasomes consist of the self-compartmentalized 20S peptidase and one or two AAA+ (ATPase associated with a variety of cellular activities) family ring hexamers. The α 7 β 7 β 7 α 7 ring topology of the 20S enzyme ensures that the proteolytic active sites, which reside in the β-subunits, are sequestered and can only cleave substrates that enter the chamber through narrow axial pores formed by the α-subunits (3). As a consequence, ATP-dependent unfolding of natively folded protein substrates by the AAA+ ring and subsequent polypeptide translocation through a narrow axial channel and into the 20S chamber are required for degradation (4).Although the 20S peptidase is the degradation module in all proteasomes, the associated AAA+ unfolding machines differ. For example, homohexamers of Mpa/Arc in actinobacteria and PAN in archaea serve as proteasomal motors, whereas a heterohexameric Rpt 1-6 ring in the 19S particle is the motor of the eukaryotic 26S proteasome (2, 5). Characteristic of type-I AAA+ enzymes, Mpa/Arc, PAN, and Rpt 1-6 subunits contain a single AAA+ module for ATP binding and hydrolysis (6). By contrast, as found in type-II AAA+ enzymes, the homohexameric Cdc48 motor in the recently discovered archaeal Cdc48·20S proteasome cont...

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“…Like ubiquitin, Pup is activated by ATP hydrolysis prior to its conjugation (18,19). However, the enzymatic mechanism of Pup activation and conjugation is altogether different from that of ubiquitin (1,20). The Pup ligase, an enzyme termed PafA (proteasomal accessory factor A), both activates and conjugates Pup to protein substrates in a two-step reaction that is typical of glutamine synthetases and ␥-glutamyl cysteine synthetases (2,14,19).…”

mentioning

confidence: 99%