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Mechanochemical basis of protein degradation by a double-ring AAA+ machine

Molecular machines containing double or single AAA+ rings power energy-dependent protein degradation and other critical cellular processes, including disaggregation and remodeling of macromolecular complexes. How the mechanical activities of double-ring and single-ring AAA+ enzymes differ is unknown...

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Detalles Bibliográficos
Autores principales: Olivares, Adrian O., Nager, Andrew R., Iosefson, Ohad, Sauer, Robert T., Baker, Tania A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190165/
https://www.ncbi.nlm.nih.gov/pubmed/25195048
http://dx.doi.org/10.1038/nsmb.2885
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author Olivares, Adrian O.
Nager, Andrew R.
Iosefson, Ohad
Sauer, Robert T.
Baker, Tania A.
author_facet Olivares, Adrian O.
Nager, Andrew R.
Iosefson, Ohad
Sauer, Robert T.
Baker, Tania A.
author_sort Olivares, Adrian O.
collection PubMed
description Molecular machines containing double or single AAA+ rings power energy-dependent protein degradation and other critical cellular processes, including disaggregation and remodeling of macromolecular complexes. How the mechanical activities of double-ring and single-ring AAA+ enzymes differ is unknown. Using single-molecule optical trapping, we determine how the double-ring ClpA enzyme from Escherichia coli mechanically degrades proteins in complex with the ClpP peptidase. We demonstrate that ClpA unfolds some protein substrates substantially faster than the single-ring ClpX enzyme, which also degrades substrates in collaboration with ClpP. We find that ClpA is a slower polypeptide translocase and moves in physical steps that are smaller and more regular than steps taken by ClpX. These direct measurements of protein unfolding and translocation define the core mechanochemical behavior of a double-ring AAA+ machine and provide insight into the degradation of proteins that unfold via metastable intermediates.
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spelling pubmed-41901652015-04-01 Mechanochemical basis of protein degradation by a double-ring AAA+ machine Olivares, Adrian O. Nager, Andrew R. Iosefson, Ohad Sauer, Robert T. Baker, Tania A. Nat Struct Mol Biol Article Molecular machines containing double or single AAA+ rings power energy-dependent protein degradation and other critical cellular processes, including disaggregation and remodeling of macromolecular complexes. How the mechanical activities of double-ring and single-ring AAA+ enzymes differ is unknown. Using single-molecule optical trapping, we determine how the double-ring ClpA enzyme from Escherichia coli mechanically degrades proteins in complex with the ClpP peptidase. We demonstrate that ClpA unfolds some protein substrates substantially faster than the single-ring ClpX enzyme, which also degrades substrates in collaboration with ClpP. We find that ClpA is a slower polypeptide translocase and moves in physical steps that are smaller and more regular than steps taken by ClpX. These direct measurements of protein unfolding and translocation define the core mechanochemical behavior of a double-ring AAA+ machine and provide insight into the degradation of proteins that unfold via metastable intermediates. 2014-09-07 2014-10 /pmc/articles/PMC4190165/ /pubmed/25195048 http://dx.doi.org/10.1038/nsmb.2885 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Olivares, Adrian O.
Nager, Andrew R.
Iosefson, Ohad
Sauer, Robert T.
Baker, Tania A.
Mechanochemical basis of protein degradation by a double-ring AAA+ machine
title Mechanochemical basis of protein degradation by a double-ring AAA+ machine
title_full Mechanochemical basis of protein degradation by a double-ring AAA+ machine
title_fullStr Mechanochemical basis of protein degradation by a double-ring AAA+ machine
title_full_unstemmed Mechanochemical basis of protein degradation by a double-ring AAA+ machine
title_short Mechanochemical basis of protein degradation by a double-ring AAA+ machine
title_sort mechanochemical basis of protein degradation by a double-ring aaa+ machine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190165/
https://www.ncbi.nlm.nih.gov/pubmed/25195048
http://dx.doi.org/10.1038/nsmb.2885
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