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Structural basis for aggregate dissolution and refolding by the Mycobacterium tuberculosis ClpB-DnaK bi-chaperone system
The M. tuberculosis (Mtb) ClpB is a protein disaggregase that helps to rejuvenate the bacterial cell. DnaK is a protein foldase that can function alone, but it can also bind to the ClpB hexamer to physically couple protein disaggregation with protein refolding, although the molecular mechanism is no...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209680/ https://www.ncbi.nlm.nih.gov/pubmed/34038719 http://dx.doi.org/10.1016/j.celrep.2021.109166 |
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author | Yin, Yanting Feng, Xiang Yu, Hongjun Fay, Allison Kovach, Amanda Glickman, Michael S. Li, Huilin |
author_facet | Yin, Yanting Feng, Xiang Yu, Hongjun Fay, Allison Kovach, Amanda Glickman, Michael S. Li, Huilin |
author_sort | Yin, Yanting |
collection | PubMed |
description | The M. tuberculosis (Mtb) ClpB is a protein disaggregase that helps to rejuvenate the bacterial cell. DnaK is a protein foldase that can function alone, but it can also bind to the ClpB hexamer to physically couple protein disaggregation with protein refolding, although the molecular mechanism is not well understood. Here, we report the cryo-EM analysis of the Mtb ClpB-DnaK bi-chaperone in the presence of ATPγS and a protein substrate. We observe three ClpB conformations in the presence of DnaK, identify a conserved TGIP loop linking the oligonucleotide/oligosaccharide-binding domain and the nucleotide-binding domain that is important for ClpB function, derive the interface between the regulatory middle domain of the ClpB and the DnaK nucleotide-binding domain, and find that DnaK binding stabilizes, but does not bend or tilt, the ClpB middle domain. We propose a model for the synergistic actions of aggregate dissolution and refolding by the Mtb ClpB-DnaK bi-chaperone system. |
format | Online Article Text |
id | pubmed-8209680 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-82096802021-06-17 Structural basis for aggregate dissolution and refolding by the Mycobacterium tuberculosis ClpB-DnaK bi-chaperone system Yin, Yanting Feng, Xiang Yu, Hongjun Fay, Allison Kovach, Amanda Glickman, Michael S. Li, Huilin Cell Rep Article The M. tuberculosis (Mtb) ClpB is a protein disaggregase that helps to rejuvenate the bacterial cell. DnaK is a protein foldase that can function alone, but it can also bind to the ClpB hexamer to physically couple protein disaggregation with protein refolding, although the molecular mechanism is not well understood. Here, we report the cryo-EM analysis of the Mtb ClpB-DnaK bi-chaperone in the presence of ATPγS and a protein substrate. We observe three ClpB conformations in the presence of DnaK, identify a conserved TGIP loop linking the oligonucleotide/oligosaccharide-binding domain and the nucleotide-binding domain that is important for ClpB function, derive the interface between the regulatory middle domain of the ClpB and the DnaK nucleotide-binding domain, and find that DnaK binding stabilizes, but does not bend or tilt, the ClpB middle domain. We propose a model for the synergistic actions of aggregate dissolution and refolding by the Mtb ClpB-DnaK bi-chaperone system. 2021-05-25 /pmc/articles/PMC8209680/ /pubmed/34038719 http://dx.doi.org/10.1016/j.celrep.2021.109166 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Yin, Yanting Feng, Xiang Yu, Hongjun Fay, Allison Kovach, Amanda Glickman, Michael S. Li, Huilin Structural basis for aggregate dissolution and refolding by the Mycobacterium tuberculosis ClpB-DnaK bi-chaperone system |
title | Structural basis for aggregate dissolution and refolding by the Mycobacterium tuberculosis ClpB-DnaK bi-chaperone system |
title_full | Structural basis for aggregate dissolution and refolding by the Mycobacterium tuberculosis ClpB-DnaK bi-chaperone system |
title_fullStr | Structural basis for aggregate dissolution and refolding by the Mycobacterium tuberculosis ClpB-DnaK bi-chaperone system |
title_full_unstemmed | Structural basis for aggregate dissolution and refolding by the Mycobacterium tuberculosis ClpB-DnaK bi-chaperone system |
title_short | Structural basis for aggregate dissolution and refolding by the Mycobacterium tuberculosis ClpB-DnaK bi-chaperone system |
title_sort | structural basis for aggregate dissolution and refolding by the mycobacterium tuberculosis clpb-dnak bi-chaperone system |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209680/ https://www.ncbi.nlm.nih.gov/pubmed/34038719 http://dx.doi.org/10.1016/j.celrep.2021.109166 |
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