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Molecular and structural insights into an asymmetric proteolytic complex (ClpP1P2) from Mycobacterium smegmatis
The ClpP protease is found in all kingdoms of life, from bacteria to humans. In general, this protease forms a homo-oligomeric complex composed of 14 identical subunits, which associates with its cognate ATPase in a symmetrical manner. Here we show that, in contrast to this general architecture, the...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889138/ https://www.ncbi.nlm.nih.gov/pubmed/31792243 http://dx.doi.org/10.1038/s41598-019-53736-8 |
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author | Nagpal, Jyotsna Paxman, Jason J. Zammit, Jessica E. Thomas, Adam A. Truscott, Kaye N. Heras, Begoña Dougan, David A. |
author_facet | Nagpal, Jyotsna Paxman, Jason J. Zammit, Jessica E. Thomas, Adam A. Truscott, Kaye N. Heras, Begoña Dougan, David A. |
author_sort | Nagpal, Jyotsna |
collection | PubMed |
description | The ClpP protease is found in all kingdoms of life, from bacteria to humans. In general, this protease forms a homo-oligomeric complex composed of 14 identical subunits, which associates with its cognate ATPase in a symmetrical manner. Here we show that, in contrast to this general architecture, the Clp protease from Mycobacterium smegmatis (Msm) forms an asymmetric hetero-oligomeric complex ClpP1P2, which only associates with its cognate ATPase through the ClpP2 ring. Our structural and functional characterisation of this complex demonstrates that asymmetric docking of the ATPase component is controlled by both the composition of the ClpP1 hydrophobic pocket (Hp) and the presence of a unique C-terminal extension in ClpP1 that guards this Hp. Our structural analysis of (Msm)ClpP1 also revealed openings in the side-walls of the inactive tetradecamer, which may represent sites for product egress. |
format | Online Article Text |
id | pubmed-6889138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68891382019-12-10 Molecular and structural insights into an asymmetric proteolytic complex (ClpP1P2) from Mycobacterium smegmatis Nagpal, Jyotsna Paxman, Jason J. Zammit, Jessica E. Thomas, Adam A. Truscott, Kaye N. Heras, Begoña Dougan, David A. Sci Rep Article The ClpP protease is found in all kingdoms of life, from bacteria to humans. In general, this protease forms a homo-oligomeric complex composed of 14 identical subunits, which associates with its cognate ATPase in a symmetrical manner. Here we show that, in contrast to this general architecture, the Clp protease from Mycobacterium smegmatis (Msm) forms an asymmetric hetero-oligomeric complex ClpP1P2, which only associates with its cognate ATPase through the ClpP2 ring. Our structural and functional characterisation of this complex demonstrates that asymmetric docking of the ATPase component is controlled by both the composition of the ClpP1 hydrophobic pocket (Hp) and the presence of a unique C-terminal extension in ClpP1 that guards this Hp. Our structural analysis of (Msm)ClpP1 also revealed openings in the side-walls of the inactive tetradecamer, which may represent sites for product egress. Nature Publishing Group UK 2019-12-02 /pmc/articles/PMC6889138/ /pubmed/31792243 http://dx.doi.org/10.1038/s41598-019-53736-8 Text en © The Author(s) 2019 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Nagpal, Jyotsna Paxman, Jason J. Zammit, Jessica E. Thomas, Adam A. Truscott, Kaye N. Heras, Begoña Dougan, David A. Molecular and structural insights into an asymmetric proteolytic complex (ClpP1P2) from Mycobacterium smegmatis |
title | Molecular and structural insights into an asymmetric proteolytic complex (ClpP1P2) from Mycobacterium smegmatis |
title_full | Molecular and structural insights into an asymmetric proteolytic complex (ClpP1P2) from Mycobacterium smegmatis |
title_fullStr | Molecular and structural insights into an asymmetric proteolytic complex (ClpP1P2) from Mycobacterium smegmatis |
title_full_unstemmed | Molecular and structural insights into an asymmetric proteolytic complex (ClpP1P2) from Mycobacterium smegmatis |
title_short | Molecular and structural insights into an asymmetric proteolytic complex (ClpP1P2) from Mycobacterium smegmatis |
title_sort | molecular and structural insights into an asymmetric proteolytic complex (clpp1p2) from mycobacterium smegmatis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889138/ https://www.ncbi.nlm.nih.gov/pubmed/31792243 http://dx.doi.org/10.1038/s41598-019-53736-8 |
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