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A novel N-terminal extension in mitochondrial TRAP1 serves as a thermal regulator of chaperone activity

Hsp90 is a conserved chaperone that facilitates protein homeostasis. Our crystal structure of the mitochondrial Hsp90, TRAP1, revealed an extension of the N-terminal β-strand previously shown to cross between protomers in the closed state. In this study, we address the regulatory function of this ex...

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Autores principales: Partridge, James R, Lavery, Laura A, Elnatan, Daniel, Naber, Nariman, Cooke, Roger, Agard, David A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381864/
https://www.ncbi.nlm.nih.gov/pubmed/25531069
http://dx.doi.org/10.7554/eLife.03487
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author Partridge, James R
Lavery, Laura A
Elnatan, Daniel
Naber, Nariman
Cooke, Roger
Agard, David A
author_facet Partridge, James R
Lavery, Laura A
Elnatan, Daniel
Naber, Nariman
Cooke, Roger
Agard, David A
author_sort Partridge, James R
collection PubMed
description Hsp90 is a conserved chaperone that facilitates protein homeostasis. Our crystal structure of the mitochondrial Hsp90, TRAP1, revealed an extension of the N-terminal β-strand previously shown to cross between protomers in the closed state. In this study, we address the regulatory function of this extension or ‘strap’ and demonstrate its responsibility for an unusual temperature dependence in ATPase rates. This dependence is a consequence of a thermally sensitive kinetic barrier between the apo ‘open’ and ATP-bound ‘closed’ conformations. The strap stabilizes the closed state through trans-protomer interactions. Displacement of cis-protomer contacts from the apo state is rate-limiting for closure and ATP hydrolysis. Strap release is coupled to rotation of the N-terminal domain and dynamics of the nucleotide binding pocket lid. The strap is conserved in higher eukaryotes but absent from yeast and prokaryotes suggesting its role as a thermal and kinetic regulator, adapting Hsp90s to the demands of unique cellular and organismal environments. DOI: http://dx.doi.org/10.7554/eLife.03487.001
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spelling pubmed-43818642015-04-03 A novel N-terminal extension in mitochondrial TRAP1 serves as a thermal regulator of chaperone activity Partridge, James R Lavery, Laura A Elnatan, Daniel Naber, Nariman Cooke, Roger Agard, David A eLife Biochemistry Hsp90 is a conserved chaperone that facilitates protein homeostasis. Our crystal structure of the mitochondrial Hsp90, TRAP1, revealed an extension of the N-terminal β-strand previously shown to cross between protomers in the closed state. In this study, we address the regulatory function of this extension or ‘strap’ and demonstrate its responsibility for an unusual temperature dependence in ATPase rates. This dependence is a consequence of a thermally sensitive kinetic barrier between the apo ‘open’ and ATP-bound ‘closed’ conformations. The strap stabilizes the closed state through trans-protomer interactions. Displacement of cis-protomer contacts from the apo state is rate-limiting for closure and ATP hydrolysis. Strap release is coupled to rotation of the N-terminal domain and dynamics of the nucleotide binding pocket lid. The strap is conserved in higher eukaryotes but absent from yeast and prokaryotes suggesting its role as a thermal and kinetic regulator, adapting Hsp90s to the demands of unique cellular and organismal environments. DOI: http://dx.doi.org/10.7554/eLife.03487.001 eLife Sciences Publications, Ltd 2014-12-22 /pmc/articles/PMC4381864/ /pubmed/25531069 http://dx.doi.org/10.7554/eLife.03487 Text en © 2014, Partridge et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biochemistry
Partridge, James R
Lavery, Laura A
Elnatan, Daniel
Naber, Nariman
Cooke, Roger
Agard, David A
A novel N-terminal extension in mitochondrial TRAP1 serves as a thermal regulator of chaperone activity
title A novel N-terminal extension in mitochondrial TRAP1 serves as a thermal regulator of chaperone activity
title_full A novel N-terminal extension in mitochondrial TRAP1 serves as a thermal regulator of chaperone activity
title_fullStr A novel N-terminal extension in mitochondrial TRAP1 serves as a thermal regulator of chaperone activity
title_full_unstemmed A novel N-terminal extension in mitochondrial TRAP1 serves as a thermal regulator of chaperone activity
title_short A novel N-terminal extension in mitochondrial TRAP1 serves as a thermal regulator of chaperone activity
title_sort novel n-terminal extension in mitochondrial trap1 serves as a thermal regulator of chaperone activity
topic Biochemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381864/
https://www.ncbi.nlm.nih.gov/pubmed/25531069
http://dx.doi.org/10.7554/eLife.03487
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