Structure, Function, and Allosteric Regulation of the 20S Proteasome by the 11S/PA28 Family of Proteasome Activators

Thomas, Taylor; Salcedo-Tacuma, David; Smith, David M.

doi:10.3390/biom13091326

Open AccessReview

Structure, Function, and Allosteric Regulation of the 20S Proteasome by the 11S/PA28 Family of Proteasome Activators

by

Taylor Thomas

^1,†,

David Salcedo-Tacuma

^1,† and

David M. Smith

^1,2,*

¹

Department of Biochemistry and Molecular Medicine, School of Medicine, West Virginia University, 64 Medical Center Drive, Morgantown, WV 26506, USA

²

Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV 26506, USA

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Biomolecules 2023, 13(9), 1326; https://doi.org/10.3390/biom13091326

Submission received: 17 July 2023 / Revised: 24 August 2023 / Accepted: 24 August 2023 / Published: 29 August 2023

(This article belongs to the Special Issue Allosteric Regulation in Ubiquitin Proteasome System)

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Abstract

The proteasome, a complex multi-catalytic protease machinery, orchestrates the protein degradation essential for maintaining cellular homeostasis, and its dysregulation also underlies many different types of diseases. Its function is regulated by many different mechanisms that encompass various factors such as proteasome activators (PAs), adaptor proteins, and post-translational modifications. This review highlights the unique characteristics of proteasomal regulation through the lens of a distinct family of regulators, the 11S, REGs, or PA26/PA28. This ATP-independent family, spanning from amoebas to mammals, exhibits a common architectural structure; yet, their cellular biology and criteria for protein degradation remain mostly elusive. We delve into their evolution and cellular biology, and contrast their structure and function comprehensively, emphasizing the unanswered questions regarding their regulatory mechanisms and broader roles in proteostasis. A deeper understanding of these processes will illuminate the roles of this regulatory family in biology and disease, thus contributing to the advancement of therapeutic strategies.

Keywords: proteasome; protein degradation; proteostasis; 11S; REGs; PA28γ

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MDPI and ACS Style

Thomas, T.; Salcedo-Tacuma, D.; Smith, D.M. Structure, Function, and Allosteric Regulation of the 20S Proteasome by the 11S/PA28 Family of Proteasome Activators. Biomolecules 2023, 13, 1326. https://doi.org/10.3390/biom13091326

AMA Style

Thomas T, Salcedo-Tacuma D, Smith DM. Structure, Function, and Allosteric Regulation of the 20S Proteasome by the 11S/PA28 Family of Proteasome Activators. Biomolecules. 2023; 13(9):1326. https://doi.org/10.3390/biom13091326

Chicago/Turabian Style

Thomas, Taylor, David Salcedo-Tacuma, and David M. Smith. 2023. "Structure, Function, and Allosteric Regulation of the 20S Proteasome by the 11S/PA28 Family of Proteasome Activators" Biomolecules 13, no. 9: 1326. https://doi.org/10.3390/biom13091326

APA Style

Thomas, T., Salcedo-Tacuma, D., & Smith, D. M. (2023). Structure, Function, and Allosteric Regulation of the 20S Proteasome by the 11S/PA28 Family of Proteasome Activators. Biomolecules, 13(9), 1326. https://doi.org/10.3390/biom13091326

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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Structure, Function, and Allosteric Regulation of the 20S Proteasome by the 11S/PA28 Family of Proteasome Activators

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