Topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease

Abstract More than one thousand knotted protein structures have been identified so far, but the functional roles of these knots remain elusive. It has been postulated that backbone entanglement may provide additional mechanostability. Here, we employed a bacterial proteasome, ClpXP, to mechanically...

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Autores principales:	Manoj Kumar Sriramoju, Yen Chen, Yun-Tzai Cloud Lee, Shang-Te Danny Hsu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fa864d0cc6a64dd7a10217775b02ea30
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spelling	oai:doaj.org-article:fa864d0cc6a64dd7a10217775b02ea302021-12-02T15:08:54ZTopologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease10.1038/s41598-018-25470-02045-2322https://doaj.org/article/fa864d0cc6a64dd7a10217775b02ea302018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25470-0https://doaj.org/toc/2045-2322Abstract More than one thousand knotted protein structures have been identified so far, but the functional roles of these knots remain elusive. It has been postulated that backbone entanglement may provide additional mechanostability. Here, we employed a bacterial proteasome, ClpXP, to mechanically unfold 52-knotted human ubiquitin C-terminal hydrolase (UCH) paralogs from their C-termini, followed by processive translocation into the proteolytic chamber for degradation. Our results revealed unprecedentedly slow kinetics of ClpXP-mediated proteolysis for the proteasome-associated UCHL5: ten thousand times slower than that of a green fluorescence protein (GFP), which has a comparable size to the UCH domain but much higher chemical and thermal stabilities. The ClpXP-dependent mechanostability positively correlates with the intrinsic unfolding rates of the substrates, spanning over several orders of magnitude for the UCHs. The broad range of mechanostability within the same protein family may be associated with the functional requirements for their differential malleabilities.Manoj Kumar SriramojuYen ChenYun-Tzai Cloud LeeShang-Te Danny HsuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Manoj Kumar Sriramoju Yen Chen Yun-Tzai Cloud Lee Shang-Te Danny Hsu Topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease
description	Abstract More than one thousand knotted protein structures have been identified so far, but the functional roles of these knots remain elusive. It has been postulated that backbone entanglement may provide additional mechanostability. Here, we employed a bacterial proteasome, ClpXP, to mechanically unfold 52-knotted human ubiquitin C-terminal hydrolase (UCH) paralogs from their C-termini, followed by processive translocation into the proteolytic chamber for degradation. Our results revealed unprecedentedly slow kinetics of ClpXP-mediated proteolysis for the proteasome-associated UCHL5: ten thousand times slower than that of a green fluorescence protein (GFP), which has a comparable size to the UCH domain but much higher chemical and thermal stabilities. The ClpXP-dependent mechanostability positively correlates with the intrinsic unfolding rates of the substrates, spanning over several orders of magnitude for the UCHs. The broad range of mechanostability within the same protein family may be associated with the functional requirements for their differential malleabilities.
format	article
author	Manoj Kumar Sriramoju Yen Chen Yun-Tzai Cloud Lee Shang-Te Danny Hsu
author_facet	Manoj Kumar Sriramoju Yen Chen Yun-Tzai Cloud Lee Shang-Te Danny Hsu
author_sort	Manoj Kumar Sriramoju
title	Topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease
title_short	Topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease
title_full	Topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease
title_fullStr	Topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease
title_full_unstemmed	Topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease
title_sort	topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an aaa+ protease
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/fa864d0cc6a64dd7a10217775b02ea30
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_version_	1718387977000845312

Topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease

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