Structural basis for the structural dynamics of human mitochondrial chaperonin mHsp60

Abstract Human mitochondrial chaperonin mHsp60 is essential for mitochondrial function by assisting folding of mitochondrial proteins. Unlike the double-ring bacterial GroEL, mHsp60 exists as a heptameric ring that is unstable and dissociates to subunits. The structural dynamics has been implicated...

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Autores principales:	Joseph Che-Yen Wang, Lingling Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/da78a54da34e4c4c96cbe02da7b7c6bd
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spelling	oai:doaj.org-article:da78a54da34e4c4c96cbe02da7b7c6bd2021-12-02T17:57:15ZStructural basis for the structural dynamics of human mitochondrial chaperonin mHsp6010.1038/s41598-021-94236-y2045-2322https://doaj.org/article/da78a54da34e4c4c96cbe02da7b7c6bd2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94236-yhttps://doaj.org/toc/2045-2322Abstract Human mitochondrial chaperonin mHsp60 is essential for mitochondrial function by assisting folding of mitochondrial proteins. Unlike the double-ring bacterial GroEL, mHsp60 exists as a heptameric ring that is unstable and dissociates to subunits. The structural dynamics has been implicated for a unique mechanism of mHsp60. We purified active heptameric mHsp60, and determined a cryo-EM structure of mHsp60 heptamer at 3.4 Å. Of the three domains, the equatorial domains contribute most to the inter-subunit interactions, which include a four-stranded β sheet. Our structural comparison with GroEL shows that mHsp60 contains several unique sequences that directly decrease the sidechain interactions around the β sheet and indirectly shorten β strands by disengaging the backbones of the flanking residues from hydrogen bonding in the β strand conformation. The decreased inter-subunit interactions result in a small inter-subunit interface in mHsp60 compared to GroEL, providing a structural basis for the dynamics of mHsp60 subunit association. Importantly, the unique sequences are conserved among higher eukaryotic mitochondrial chaperonins, suggesting the importance of structural dynamics for eukaryotic chaperonins. Our structural comparison with the single-ring mHsp60-mHsp10 shows that upon mHsp10 binding the shortened inter-subunit β sheet is restored and the overall inter-subunit interface of mHsp60 increases drastically. Our structural basis for the mHsp10 induced stabilization of mHsp60 subunit interaction is consistent with the literature that mHsp10 stabilizes mHsp60 quaternary structure. Together, our studies provide structural bases for structural dynamics of the mHsp60 heptamer and for the stabilizing effect of mHsp10 on mHsp60 subunit association.Joseph Che-Yen WangLingling ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joseph Che-Yen Wang Lingling Chen Structural basis for the structural dynamics of human mitochondrial chaperonin mHsp60
description	Abstract Human mitochondrial chaperonin mHsp60 is essential for mitochondrial function by assisting folding of mitochondrial proteins. Unlike the double-ring bacterial GroEL, mHsp60 exists as a heptameric ring that is unstable and dissociates to subunits. The structural dynamics has been implicated for a unique mechanism of mHsp60. We purified active heptameric mHsp60, and determined a cryo-EM structure of mHsp60 heptamer at 3.4 Å. Of the three domains, the equatorial domains contribute most to the inter-subunit interactions, which include a four-stranded β sheet. Our structural comparison with GroEL shows that mHsp60 contains several unique sequences that directly decrease the sidechain interactions around the β sheet and indirectly shorten β strands by disengaging the backbones of the flanking residues from hydrogen bonding in the β strand conformation. The decreased inter-subunit interactions result in a small inter-subunit interface in mHsp60 compared to GroEL, providing a structural basis for the dynamics of mHsp60 subunit association. Importantly, the unique sequences are conserved among higher eukaryotic mitochondrial chaperonins, suggesting the importance of structural dynamics for eukaryotic chaperonins. Our structural comparison with the single-ring mHsp60-mHsp10 shows that upon mHsp10 binding the shortened inter-subunit β sheet is restored and the overall inter-subunit interface of mHsp60 increases drastically. Our structural basis for the mHsp10 induced stabilization of mHsp60 subunit interaction is consistent with the literature that mHsp10 stabilizes mHsp60 quaternary structure. Together, our studies provide structural bases for structural dynamics of the mHsp60 heptamer and for the stabilizing effect of mHsp10 on mHsp60 subunit association.
format	article
author	Joseph Che-Yen Wang Lingling Chen
author_facet	Joseph Che-Yen Wang Lingling Chen
author_sort	Joseph Che-Yen Wang
title	Structural basis for the structural dynamics of human mitochondrial chaperonin mHsp60
title_short	Structural basis for the structural dynamics of human mitochondrial chaperonin mHsp60
title_full	Structural basis for the structural dynamics of human mitochondrial chaperonin mHsp60
title_fullStr	Structural basis for the structural dynamics of human mitochondrial chaperonin mHsp60
title_full_unstemmed	Structural basis for the structural dynamics of human mitochondrial chaperonin mHsp60
title_sort	structural basis for the structural dynamics of human mitochondrial chaperonin mhsp60
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/da78a54da34e4c4c96cbe02da7b7c6bd
work_keys_str_mv	AT josephcheyenwang structuralbasisforthestructuraldynamicsofhumanmitochondrialchaperoninmhsp60 AT linglingchen structuralbasisforthestructuraldynamicsofhumanmitochondrialchaperoninmhsp60
_version_	1718379077369331712

Structural basis for the structural dynamics of human mitochondrial chaperonin mHsp60

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