Allosteric Effects in the Regulation of 26S Proteasome Activities

The 26S proteasome is the executive arm of the ubiquitin-proteasome system. This 2.5-MDa complex comprising the 20S core particle (CP) and the 19S regulatory particle (RP) is able to effectively execute its function due to a tightly regulated network of allosteric interactions. From this perspective...

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Bibliographic Details
Published in:Journal of molecular biology 2013-05, Vol.425 (9), p.1415-1423
Main Authors: Śledź, Paweł, Förster, Friedrich, Baumeister, Wolfgang
Format: Article
Language:English
Subjects:
26S proteasome
Adenosine Triphosphatases - chemistry
Adenosine Triphosphatases - metabolism
adenosine triphosphate
Allosteric Regulation
allostery
cryo-electron microscopy
Escherichia coli Proteins - chemistry
Escherichia coli Proteins - metabolism
Humans
hydrolysis
Models, Molecular
proteasome endopeptidase complex
Proteasome Endopeptidase Complex - chemistry
Proteasome Endopeptidase Complex - metabolism
proteolysis
proteostasis
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Summary:The 26S proteasome is the executive arm of the ubiquitin-proteasome system. This 2.5-MDa complex comprising the 20S core particle (CP) and the 19S regulatory particle (RP) is able to effectively execute its function due to a tightly regulated network of allosteric interactions. From this perspective, we summarize the current state of knowledge on these regulatory interdependencies. We classify them into the three functional layers—within the CP, within the RP, and at the CP–RP interface. In the CP, allosteric effects are thought to couple the gate opening and substrate proteolysis. Gate opening depends on events occurring in the RP—ATP hydrolysis and substrate binding. Finally, a number of processes occurring solely in the RP, like ATP hydrolysis or substrate deubiquitylation, are also proposed to be allosterically regulated. Recent advances in structural studies of 26S proteasome open up new avenues for dissecting and rationalizing the molecular basis of these regulatory networks. [Display omitted] ► 26S proteasome executes its function in proteostasis, thanks to the allosteric regulation. ► Several distinct layers of regulation are present within the 26S proteasome. ► Cryo-electron microscopy to elucidate the mechanisms of allosteric events within the proteasome.
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2013.01.036