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AAA+ Machines of Protein Destruction in Mycobacteria

The bacterial cytosol is a complex mixture of macromolecules (proteins, DNA, and RNA), which collectively are responsible for an enormous array of cellular tasks. Proteins are central to most, if not all, of these tasks and as such their maintenance (commonly referred to as protein homeostasis or pr...

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Autores principales: Alhuwaider, Adnan Ali H., Dougan, David A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515868/
https://www.ncbi.nlm.nih.gov/pubmed/28770209
http://dx.doi.org/10.3389/fmolb.2017.00049
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author Alhuwaider, Adnan Ali H.
Dougan, David A.
author_facet Alhuwaider, Adnan Ali H.
Dougan, David A.
author_sort Alhuwaider, Adnan Ali H.
collection PubMed
description The bacterial cytosol is a complex mixture of macromolecules (proteins, DNA, and RNA), which collectively are responsible for an enormous array of cellular tasks. Proteins are central to most, if not all, of these tasks and as such their maintenance (commonly referred to as protein homeostasis or proteostasis) is vital for cell survival during normal and stressful conditions. The two key aspects of protein homeostasis are, (i) the correct folding and assembly of proteins (coupled with their delivery to the correct cellular location) and (ii) the timely removal of unwanted or damaged proteins from the cell, which are performed by molecular chaperones and proteases, respectively. A major class of proteins that contribute to both of these tasks are the AAA+ (ATPases associated with a variety of cellular activities) protein superfamily. Although much is known about the structure of these machines and how they function in the model Gram-negative bacterium Escherichia coli, we are only just beginning to discover the molecular details of these machines and how they function in mycobacteria. Here we review the different AAA+ machines, that contribute to proteostasis in mycobacteria. Primarily we will focus on the recent advances in the structure and function of AAA+ proteases, the substrates they recognize and the cellular pathways they control. Finally, we will discuss the recent developments related to these machines as novel drug targets.
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spelling pubmed-55158682017-08-02 AAA+ Machines of Protein Destruction in Mycobacteria Alhuwaider, Adnan Ali H. Dougan, David A. Front Mol Biosci Molecular Biosciences The bacterial cytosol is a complex mixture of macromolecules (proteins, DNA, and RNA), which collectively are responsible for an enormous array of cellular tasks. Proteins are central to most, if not all, of these tasks and as such their maintenance (commonly referred to as protein homeostasis or proteostasis) is vital for cell survival during normal and stressful conditions. The two key aspects of protein homeostasis are, (i) the correct folding and assembly of proteins (coupled with their delivery to the correct cellular location) and (ii) the timely removal of unwanted or damaged proteins from the cell, which are performed by molecular chaperones and proteases, respectively. A major class of proteins that contribute to both of these tasks are the AAA+ (ATPases associated with a variety of cellular activities) protein superfamily. Although much is known about the structure of these machines and how they function in the model Gram-negative bacterium Escherichia coli, we are only just beginning to discover the molecular details of these machines and how they function in mycobacteria. Here we review the different AAA+ machines, that contribute to proteostasis in mycobacteria. Primarily we will focus on the recent advances in the structure and function of AAA+ proteases, the substrates they recognize and the cellular pathways they control. Finally, we will discuss the recent developments related to these machines as novel drug targets. Frontiers Media S.A. 2017-07-19 /pmc/articles/PMC5515868/ /pubmed/28770209 http://dx.doi.org/10.3389/fmolb.2017.00049 Text en Copyright © 2017 Alhuwaider and Dougan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Alhuwaider, Adnan Ali H.
Dougan, David A.
AAA+ Machines of Protein Destruction in Mycobacteria
title AAA+ Machines of Protein Destruction in Mycobacteria
title_full AAA+ Machines of Protein Destruction in Mycobacteria
title_fullStr AAA+ Machines of Protein Destruction in Mycobacteria
title_full_unstemmed AAA+ Machines of Protein Destruction in Mycobacteria
title_short AAA+ Machines of Protein Destruction in Mycobacteria
title_sort aaa+ machines of protein destruction in mycobacteria
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515868/
https://www.ncbi.nlm.nih.gov/pubmed/28770209
http://dx.doi.org/10.3389/fmolb.2017.00049
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