Crystal structure of P. falciparum Cpn60 bound to ATP reveals an open dynamic conformation before substrate binding

Abstract Plasmodium falciparum harbors group 1 and group 2 chaperonin systems to mediate the folding of cellular proteins in different cellular locations. Two distinct group 1 chaperonins operate in the organelles of mitochondria and apicoplasts, while group 2 chaperonins function in the cytosol. No...

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Autores principales:	Brian Nguyen, Rui Ma, Wai Kwan Tang, Dashuang Shi, Niraj H. Tolia
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b980ac26f71944b9a0f7ac229bc5e405
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spelling	oai:doaj.org-article:b980ac26f71944b9a0f7ac229bc5e4052021-12-02T16:31:11ZCrystal structure of P. falciparum Cpn60 bound to ATP reveals an open dynamic conformation before substrate binding10.1038/s41598-021-85197-32045-2322https://doaj.org/article/b980ac26f71944b9a0f7ac229bc5e4052021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85197-3https://doaj.org/toc/2045-2322Abstract Plasmodium falciparum harbors group 1 and group 2 chaperonin systems to mediate the folding of cellular proteins in different cellular locations. Two distinct group 1 chaperonins operate in the organelles of mitochondria and apicoplasts, while group 2 chaperonins function in the cytosol. No structural information has been reported for any chaperonin from plasmodium. In this study, we describe the crystal structure of a double heptameric ring Plasmodium falciparum mitochondrial chaperonin 60 (Cpn60) bound with ATP, which differs significantly from any known crystal structure of chaperonin 60. The structure likely represents a unique intermediate state during conformational conversion from the closed state to the opened state. Three of the seven apical domains are highly dynamic while the equatorial domains form a stable ring. The structure implies large movements of the apical domain in the solution play a role in nucleotide-dependent regulation of substrate binding and folding. A unique 26–27 residue insertion in the equatorial domain of Plasmodium falciparum mitochondrial chaperonin greatly increases both inter-ring and intra-ring subunit–subunit interactions. The present structure provides new insights into the mechanism of Cpn60 in chaperonin assembly and function.Brian NguyenRui MaWai Kwan TangDashuang ShiNiraj H. ToliaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Brian Nguyen Rui Ma Wai Kwan Tang Dashuang Shi Niraj H. Tolia Crystal structure of P. falciparum Cpn60 bound to ATP reveals an open dynamic conformation before substrate binding
description	Abstract Plasmodium falciparum harbors group 1 and group 2 chaperonin systems to mediate the folding of cellular proteins in different cellular locations. Two distinct group 1 chaperonins operate in the organelles of mitochondria and apicoplasts, while group 2 chaperonins function in the cytosol. No structural information has been reported for any chaperonin from plasmodium. In this study, we describe the crystal structure of a double heptameric ring Plasmodium falciparum mitochondrial chaperonin 60 (Cpn60) bound with ATP, which differs significantly from any known crystal structure of chaperonin 60. The structure likely represents a unique intermediate state during conformational conversion from the closed state to the opened state. Three of the seven apical domains are highly dynamic while the equatorial domains form a stable ring. The structure implies large movements of the apical domain in the solution play a role in nucleotide-dependent regulation of substrate binding and folding. A unique 26–27 residue insertion in the equatorial domain of Plasmodium falciparum mitochondrial chaperonin greatly increases both inter-ring and intra-ring subunit–subunit interactions. The present structure provides new insights into the mechanism of Cpn60 in chaperonin assembly and function.
format	article
author	Brian Nguyen Rui Ma Wai Kwan Tang Dashuang Shi Niraj H. Tolia
author_facet	Brian Nguyen Rui Ma Wai Kwan Tang Dashuang Shi Niraj H. Tolia
author_sort	Brian Nguyen
title	Crystal structure of P. falciparum Cpn60 bound to ATP reveals an open dynamic conformation before substrate binding
title_short	Crystal structure of P. falciparum Cpn60 bound to ATP reveals an open dynamic conformation before substrate binding
title_full	Crystal structure of P. falciparum Cpn60 bound to ATP reveals an open dynamic conformation before substrate binding
title_fullStr	Crystal structure of P. falciparum Cpn60 bound to ATP reveals an open dynamic conformation before substrate binding
title_full_unstemmed	Crystal structure of P. falciparum Cpn60 bound to ATP reveals an open dynamic conformation before substrate binding
title_sort	crystal structure of p. falciparum cpn60 bound to atp reveals an open dynamic conformation before substrate binding
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b980ac26f71944b9a0f7ac229bc5e405
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Crystal structure of P. falciparum Cpn60 bound to ATP reveals an open dynamic conformation before substrate binding

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