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Head-to-tail interactions of the coiled-coil domains regulate ClpB activity and cooperation with Hsp70 in protein disaggregation
The hexameric AAA+ chaperone ClpB reactivates aggregated proteins in cooperation with the Hsp70 system. Essential for disaggregation, the ClpB middle domain (MD) is a coiled-coil propeller that binds Hsp70. Although the ClpB subunit structure is known, positioning of the MD in the hexamer and its me...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023160/ https://www.ncbi.nlm.nih.gov/pubmed/24843029 http://dx.doi.org/10.7554/eLife.02481 |
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author | Carroni, Marta Kummer, Eva Oguchi, Yuki Wendler, Petra Clare, Daniel K Sinning, Irmgard Kopp, Jürgen Mogk, Axel Bukau, Bernd Saibil, Helen R |
author_facet | Carroni, Marta Kummer, Eva Oguchi, Yuki Wendler, Petra Clare, Daniel K Sinning, Irmgard Kopp, Jürgen Mogk, Axel Bukau, Bernd Saibil, Helen R |
author_sort | Carroni, Marta |
collection | PubMed |
description | The hexameric AAA+ chaperone ClpB reactivates aggregated proteins in cooperation with the Hsp70 system. Essential for disaggregation, the ClpB middle domain (MD) is a coiled-coil propeller that binds Hsp70. Although the ClpB subunit structure is known, positioning of the MD in the hexamer and its mechanism of action are unclear. We obtained electron microscopy (EM) structures of the BAP variant of ClpB that binds the protease ClpP, clearly revealing MD density on the surface of the ClpB ring. Mutant analysis and asymmetric reconstructions show that MDs adopt diverse positions in a single ClpB hexamer. Adjacent, horizontally oriented MDs form head-to-tail contacts and repress ClpB activity by preventing Hsp70 interaction. Tilting of the MD breaks this contact, allowing Hsp70 binding, and releasing the contact in adjacent subunits. Our data suggest a wavelike activation of ClpB subunits around the ring. DOI: http://dx.doi.org/10.7554/eLife.02481.001 |
format | Online Article Text |
id | pubmed-4023160 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-40231602014-05-22 Head-to-tail interactions of the coiled-coil domains regulate ClpB activity and cooperation with Hsp70 in protein disaggregation Carroni, Marta Kummer, Eva Oguchi, Yuki Wendler, Petra Clare, Daniel K Sinning, Irmgard Kopp, Jürgen Mogk, Axel Bukau, Bernd Saibil, Helen R eLife Biochemistry The hexameric AAA+ chaperone ClpB reactivates aggregated proteins in cooperation with the Hsp70 system. Essential for disaggregation, the ClpB middle domain (MD) is a coiled-coil propeller that binds Hsp70. Although the ClpB subunit structure is known, positioning of the MD in the hexamer and its mechanism of action are unclear. We obtained electron microscopy (EM) structures of the BAP variant of ClpB that binds the protease ClpP, clearly revealing MD density on the surface of the ClpB ring. Mutant analysis and asymmetric reconstructions show that MDs adopt diverse positions in a single ClpB hexamer. Adjacent, horizontally oriented MDs form head-to-tail contacts and repress ClpB activity by preventing Hsp70 interaction. Tilting of the MD breaks this contact, allowing Hsp70 binding, and releasing the contact in adjacent subunits. Our data suggest a wavelike activation of ClpB subunits around the ring. DOI: http://dx.doi.org/10.7554/eLife.02481.001 eLife Sciences Publications, Ltd 2014-04-30 /pmc/articles/PMC4023160/ /pubmed/24843029 http://dx.doi.org/10.7554/eLife.02481 Text en Copyright © 2014, Carroni et al http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry Carroni, Marta Kummer, Eva Oguchi, Yuki Wendler, Petra Clare, Daniel K Sinning, Irmgard Kopp, Jürgen Mogk, Axel Bukau, Bernd Saibil, Helen R Head-to-tail interactions of the coiled-coil domains regulate ClpB activity and cooperation with Hsp70 in protein disaggregation |
title | Head-to-tail interactions of the coiled-coil domains regulate ClpB activity and cooperation with Hsp70 in protein disaggregation |
title_full | Head-to-tail interactions of the coiled-coil domains regulate ClpB activity and cooperation with Hsp70 in protein disaggregation |
title_fullStr | Head-to-tail interactions of the coiled-coil domains regulate ClpB activity and cooperation with Hsp70 in protein disaggregation |
title_full_unstemmed | Head-to-tail interactions of the coiled-coil domains regulate ClpB activity and cooperation with Hsp70 in protein disaggregation |
title_short | Head-to-tail interactions of the coiled-coil domains regulate ClpB activity and cooperation with Hsp70 in protein disaggregation |
title_sort | head-to-tail interactions of the coiled-coil domains regulate clpb activity and cooperation with hsp70 in protein disaggregation |
topic | Biochemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023160/ https://www.ncbi.nlm.nih.gov/pubmed/24843029 http://dx.doi.org/10.7554/eLife.02481 |
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