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Regulation of chaperone function by coupled folding and oligomerization

The homotrimeric molecular chaperone Skp of Gram-negative bacteria facilitates the transport of outer membrane proteins across the periplasm. It has been unclear how its activity is modulated during its functional cycle. Here, we report an atomic-resolution characterization of the Escherichia coli S...

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Autores principales: Mas, Guillaume, Burmann, Björn M., Sharpe, Timothy, Claudi, Beatrice, Bumann, Dirk, Hiller, Sebastian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577714/
https://www.ncbi.nlm.nih.gov/pubmed/33087350
http://dx.doi.org/10.1126/sciadv.abc5822
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author Mas, Guillaume
Burmann, Björn M.
Sharpe, Timothy
Claudi, Beatrice
Bumann, Dirk
Hiller, Sebastian
author_facet Mas, Guillaume
Burmann, Björn M.
Sharpe, Timothy
Claudi, Beatrice
Bumann, Dirk
Hiller, Sebastian
author_sort Mas, Guillaume
collection PubMed
description The homotrimeric molecular chaperone Skp of Gram-negative bacteria facilitates the transport of outer membrane proteins across the periplasm. It has been unclear how its activity is modulated during its functional cycle. Here, we report an atomic-resolution characterization of the Escherichia coli Skp monomer-trimer transition. We find that the monomeric state of Skp is intrinsically disordered and that formation of the oligomerization interface initiates folding of the α-helical coiled-coil arms via a unique “stapling” mechanism, resulting in the formation of active trimeric Skp. Native client proteins contact all three Skp subunits simultaneously, and accordingly, their binding shifts the Skp population toward the active trimer. This activation mechanism is shown to be essential for Salmonella fitness in a mouse infection model. The coupled mechanism is a unique example of how an ATP-independent chaperone can modulate its activity as a function of the presence of client proteins.
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spelling pubmed-75777142020-11-02 Regulation of chaperone function by coupled folding and oligomerization Mas, Guillaume Burmann, Björn M. Sharpe, Timothy Claudi, Beatrice Bumann, Dirk Hiller, Sebastian Sci Adv Research Articles The homotrimeric molecular chaperone Skp of Gram-negative bacteria facilitates the transport of outer membrane proteins across the periplasm. It has been unclear how its activity is modulated during its functional cycle. Here, we report an atomic-resolution characterization of the Escherichia coli Skp monomer-trimer transition. We find that the monomeric state of Skp is intrinsically disordered and that formation of the oligomerization interface initiates folding of the α-helical coiled-coil arms via a unique “stapling” mechanism, resulting in the formation of active trimeric Skp. Native client proteins contact all three Skp subunits simultaneously, and accordingly, their binding shifts the Skp population toward the active trimer. This activation mechanism is shown to be essential for Salmonella fitness in a mouse infection model. The coupled mechanism is a unique example of how an ATP-independent chaperone can modulate its activity as a function of the presence of client proteins. American Association for the Advancement of Science 2020-10-21 /pmc/articles/PMC7577714/ /pubmed/33087350 http://dx.doi.org/10.1126/sciadv.abc5822 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Mas, Guillaume
Burmann, Björn M.
Sharpe, Timothy
Claudi, Beatrice
Bumann, Dirk
Hiller, Sebastian
Regulation of chaperone function by coupled folding and oligomerization
title Regulation of chaperone function by coupled folding and oligomerization
title_full Regulation of chaperone function by coupled folding and oligomerization
title_fullStr Regulation of chaperone function by coupled folding and oligomerization
title_full_unstemmed Regulation of chaperone function by coupled folding and oligomerization
title_short Regulation of chaperone function by coupled folding and oligomerization
title_sort regulation of chaperone function by coupled folding and oligomerization
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577714/
https://www.ncbi.nlm.nih.gov/pubmed/33087350
http://dx.doi.org/10.1126/sciadv.abc5822
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