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...
Autores principales: | , |
---|---|
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 |
_version_ | 1783534279028899840 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7226402 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT zhangshuwen aaaatpasesinproteindegradationstructuresfunctionsandmechanisms AT maoyoudong aaaatpasesinproteindegradationstructuresfunctionsandmechanisms |