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Open and compressed conformations of Francisella tularensis ClpP

Caseinolytic proteases are large oligomeric assemblies responsible for maintaining protein homeostasis in bacteria and in so doing influence a wide range of biological processes. The functional assembly involves three chaperones together with the oligomeric caseinolytic protease catalytic subunit P...

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Detalles Bibliográficos
Autores principales: Díaz‐Sáez, Laura, Pankov, Genady, Hunter, William N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225881/
https://www.ncbi.nlm.nih.gov/pubmed/27802578
http://dx.doi.org/10.1002/prot.25197
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author Díaz‐Sáez, Laura
Pankov, Genady
Hunter, William N.
author_facet Díaz‐Sáez, Laura
Pankov, Genady
Hunter, William N.
author_sort Díaz‐Sáez, Laura
collection PubMed
description Caseinolytic proteases are large oligomeric assemblies responsible for maintaining protein homeostasis in bacteria and in so doing influence a wide range of biological processes. The functional assembly involves three chaperones together with the oligomeric caseinolytic protease catalytic subunit P (ClpP). This protease represents a potential target for therapeutic intervention in pathogenic bacteria. Here, we detail an efficient protocol for production of recombinant ClpP from Francisella tularensis, and the structural characterization of three crystal forms which grow under similar conditions. One crystal form reveals a compressed state of the ClpP tetradecamer and two forms an open state. A comparison of the two types of structure infers that differences at the enzyme active site result from a conformational change involving a highly localized disorder‐order transition of a β‐strand α‐helix combination. This transition occurs at a subunit‐subunit interface. Our study may now underpin future efforts in a structure‐based approach to target ClpP for inhibitor or activator development. Proteins 2016; 85:188–194. © 2016 Wiley Periodicals, Inc.
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spelling pubmed-52258812017-01-24 Open and compressed conformations of Francisella tularensis ClpP Díaz‐Sáez, Laura Pankov, Genady Hunter, William N. Proteins Structure Notes Caseinolytic proteases are large oligomeric assemblies responsible for maintaining protein homeostasis in bacteria and in so doing influence a wide range of biological processes. The functional assembly involves three chaperones together with the oligomeric caseinolytic protease catalytic subunit P (ClpP). This protease represents a potential target for therapeutic intervention in pathogenic bacteria. Here, we detail an efficient protocol for production of recombinant ClpP from Francisella tularensis, and the structural characterization of three crystal forms which grow under similar conditions. One crystal form reveals a compressed state of the ClpP tetradecamer and two forms an open state. A comparison of the two types of structure infers that differences at the enzyme active site result from a conformational change involving a highly localized disorder‐order transition of a β‐strand α‐helix combination. This transition occurs at a subunit‐subunit interface. Our study may now underpin future efforts in a structure‐based approach to target ClpP for inhibitor or activator development. Proteins 2016; 85:188–194. © 2016 Wiley Periodicals, Inc. John Wiley and Sons Inc. 2016-11-20 2017-01 /pmc/articles/PMC5225881/ /pubmed/27802578 http://dx.doi.org/10.1002/prot.25197 Text en © 2016 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Structure Notes
Díaz‐Sáez, Laura
Pankov, Genady
Hunter, William N.
Open and compressed conformations of Francisella tularensis ClpP
title Open and compressed conformations of Francisella tularensis ClpP
title_full Open and compressed conformations of Francisella tularensis ClpP
title_fullStr Open and compressed conformations of Francisella tularensis ClpP
title_full_unstemmed Open and compressed conformations of Francisella tularensis ClpP
title_short Open and compressed conformations of Francisella tularensis ClpP
title_sort open and compressed conformations of francisella tularensis clpp
topic Structure Notes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225881/
https://www.ncbi.nlm.nih.gov/pubmed/27802578
http://dx.doi.org/10.1002/prot.25197
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