AAA+ ATPases in Protein Degradation: Structures, Functions and Mechanisms

Adenosine triphosphatases (ATPases) associated with a variety of cellular activities (AAA+), the hexameric ring-shaped motor complexes located in all ATP-driven proteolytic machines, are involved in many cellular processes. Powered by cycles of ATP binding and hydrolysis, conformational changes in A...

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Autores principales: Zhang, Shuwen, Mao, Youdong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226402/
https://www.ncbi.nlm.nih.gov/pubmed/32325699
http://dx.doi.org/10.3390/biom10040629
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author Zhang, Shuwen
Mao, Youdong
author_facet Zhang, Shuwen
Mao, Youdong
author_sort Zhang, Shuwen
collection PubMed
description Adenosine triphosphatases (ATPases) associated with a variety of cellular activities (AAA+), the hexameric ring-shaped motor complexes located in all ATP-driven proteolytic machines, are involved in many cellular processes. Powered by cycles of ATP binding and hydrolysis, conformational changes in AAA+ ATPases can generate mechanical work that unfolds a substrate protein inside the central axial channel of ATPase ring for degradation. Three-dimensional visualizations of several AAA+ ATPase complexes in the act of substrate processing for protein degradation have been resolved at the atomic level thanks to recent technical advances in cryogenic electron microscopy (cryo-EM). Here, we summarize the resulting advances in structural and biochemical studies of AAA+ proteases in the process of proteolysis reactions, with an emphasis on cryo-EM structural analyses of the 26S proteasome, Cdc48/p97 and FtsH-like mitochondrial proteases. These studies reveal three highly conserved patterns in the structure–function relationship of AAA+ ATPase hexamers that were observed in the human 26S proteasome, thus suggesting common dynamic models of mechanochemical coupling during force generation and substrate translocation.
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spelling pubmed-72264022020-05-18 AAA+ ATPases in Protein Degradation: Structures, Functions and Mechanisms Zhang, Shuwen Mao, Youdong Biomolecules Review Adenosine triphosphatases (ATPases) associated with a variety of cellular activities (AAA+), the hexameric ring-shaped motor complexes located in all ATP-driven proteolytic machines, are involved in many cellular processes. Powered by cycles of ATP binding and hydrolysis, conformational changes in AAA+ ATPases can generate mechanical work that unfolds a substrate protein inside the central axial channel of ATPase ring for degradation. Three-dimensional visualizations of several AAA+ ATPase complexes in the act of substrate processing for protein degradation have been resolved at the atomic level thanks to recent technical advances in cryogenic electron microscopy (cryo-EM). Here, we summarize the resulting advances in structural and biochemical studies of AAA+ proteases in the process of proteolysis reactions, with an emphasis on cryo-EM structural analyses of the 26S proteasome, Cdc48/p97 and FtsH-like mitochondrial proteases. These studies reveal three highly conserved patterns in the structure–function relationship of AAA+ ATPase hexamers that were observed in the human 26S proteasome, thus suggesting common dynamic models of mechanochemical coupling during force generation and substrate translocation. MDPI 2020-04-18 /pmc/articles/PMC7226402/ /pubmed/32325699 http://dx.doi.org/10.3390/biom10040629 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Zhang, Shuwen
Mao, Youdong
AAA+ ATPases in Protein Degradation: Structures, Functions and Mechanisms
title AAA+ ATPases in Protein Degradation: Structures, Functions and Mechanisms
title_full AAA+ ATPases in Protein Degradation: Structures, Functions and Mechanisms
title_fullStr AAA+ ATPases in Protein Degradation: Structures, Functions and Mechanisms
title_full_unstemmed AAA+ ATPases in Protein Degradation: Structures, Functions and Mechanisms
title_short AAA+ ATPases in Protein Degradation: Structures, Functions and Mechanisms
title_sort aaa+ atpases in protein degradation: structures, functions and mechanisms
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226402/
https://www.ncbi.nlm.nih.gov/pubmed/32325699
http://dx.doi.org/10.3390/biom10040629
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