Structure of the human TRiC/CCT Subunit 5 associated with hereditary sensory neuropathy

Abstract The human chaperonin TRiC consists of eight non-identical subunits, and its protein-folding activity is critical for cellular health. Misfolded proteins are associated with many human diseases, such as amyloid diseases, cancer, and neuropathies, making TRiC a potential therapeutic target. A...

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Autores principales:	Jose H. Pereira, Ryan P. McAndrew, Oksana A. Sergeeva, Corie Y. Ralston, Jonathan A. King, Paul D. Adams
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/380cea13dfbc4d1c99c09ee67ecb6f29
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spelling	oai:doaj.org-article:380cea13dfbc4d1c99c09ee67ecb6f292021-12-02T11:53:06ZStructure of the human TRiC/CCT Subunit 5 associated with hereditary sensory neuropathy10.1038/s41598-017-03825-32045-2322https://doaj.org/article/380cea13dfbc4d1c99c09ee67ecb6f292017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03825-3https://doaj.org/toc/2045-2322Abstract The human chaperonin TRiC consists of eight non-identical subunits, and its protein-folding activity is critical for cellular health. Misfolded proteins are associated with many human diseases, such as amyloid diseases, cancer, and neuropathies, making TRiC a potential therapeutic target. A detailed structural understanding of its ATP-dependent folding mechanism and substrate recognition is therefore of great importance. Of particular health-related interest is the mutation Histidine 147 to Arginine (H147R) in human TRiC subunit 5 (CCT5), which has been associated with hereditary sensory neuropathy. In this paper, we describe the crystal structures of CCT5 and the CCT5-H147R mutant, which provide important structural information for this vital protein-folding machine in humans. This first X-ray crystallographic study of a single human CCT subunit in the context of a hexadecameric complex can be expanded in the future to the other 7 subunits that form the TRiC complex.Jose H. PereiraRyan P. McAndrewOksana A. SergeevaCorie Y. RalstonJonathan A. KingPaul D. AdamsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jose H. Pereira Ryan P. McAndrew Oksana A. Sergeeva Corie Y. Ralston Jonathan A. King Paul D. Adams Structure of the human TRiC/CCT Subunit 5 associated with hereditary sensory neuropathy
description	Abstract The human chaperonin TRiC consists of eight non-identical subunits, and its protein-folding activity is critical for cellular health. Misfolded proteins are associated with many human diseases, such as amyloid diseases, cancer, and neuropathies, making TRiC a potential therapeutic target. A detailed structural understanding of its ATP-dependent folding mechanism and substrate recognition is therefore of great importance. Of particular health-related interest is the mutation Histidine 147 to Arginine (H147R) in human TRiC subunit 5 (CCT5), which has been associated with hereditary sensory neuropathy. In this paper, we describe the crystal structures of CCT5 and the CCT5-H147R mutant, which provide important structural information for this vital protein-folding machine in humans. This first X-ray crystallographic study of a single human CCT subunit in the context of a hexadecameric complex can be expanded in the future to the other 7 subunits that form the TRiC complex.
format	article
author	Jose H. Pereira Ryan P. McAndrew Oksana A. Sergeeva Corie Y. Ralston Jonathan A. King Paul D. Adams
author_facet	Jose H. Pereira Ryan P. McAndrew Oksana A. Sergeeva Corie Y. Ralston Jonathan A. King Paul D. Adams
author_sort	Jose H. Pereira
title	Structure of the human TRiC/CCT Subunit 5 associated with hereditary sensory neuropathy
title_short	Structure of the human TRiC/CCT Subunit 5 associated with hereditary sensory neuropathy
title_full	Structure of the human TRiC/CCT Subunit 5 associated with hereditary sensory neuropathy
title_fullStr	Structure of the human TRiC/CCT Subunit 5 associated with hereditary sensory neuropathy
title_full_unstemmed	Structure of the human TRiC/CCT Subunit 5 associated with hereditary sensory neuropathy
title_sort	structure of the human tric/cct subunit 5 associated with hereditary sensory neuropathy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/380cea13dfbc4d1c99c09ee67ecb6f29
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_version_	1718394860320325632

Structure of the human TRiC/CCT Subunit 5 associated with hereditary sensory neuropathy

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