Architecture and assembly of the archaeal Cdc48*20S proteasome
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Barthelme-2014-Architecture and ass.pdf
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Author(s)
Barthelme, Dominik
Chen, James Z.
Grabenstatter, Jonathan Dean
Baker, Tania
Sauer, Robert T
Date Issued
April 2014
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Barthelme, Dominik, James Z. Chen, Jonathan Grabenstatter, Tania A. Baker, and Robert T. Sauer. “Architecture and Assembly of the Archaeal Cdc48*20S Proteasome.” Proceedings of the National Academy of Sciences 111, no. 17 (April 7, 2014): E1687–E1694.
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Earth, Atmospheric, and Planetary Sciences
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Earth, Atmospheric, and Planetary Sciences
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1404823111
