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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2021-03-01
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doaj-b980ac26f71944b9a0f7ac229bc5e4052021-03-21T12:38:57ZengNature Publishing GroupScientific Reports2045-23222021-03-0111111510.1038/s41598-021-85197-3Crystal structure of P. falciparum Cpn60 bound to ATP reveals an open dynamic conformation before substrate bindingBrian Nguyen0Rui Ma1Wai Kwan Tang2Dashuang Shi3Niraj H. Tolia4Host-Pathogen Interactions and Structural Vaccinology Section, Laboratory of Malaria Immunology and Vaccinology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of HealthHost-Pathogen Interactions and Structural Vaccinology Section, Laboratory of Malaria Immunology and Vaccinology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of HealthHost-Pathogen Interactions and Structural Vaccinology Section, Laboratory of Malaria Immunology and Vaccinology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of HealthHost-Pathogen Interactions and Structural Vaccinology Section, Laboratory of Malaria Immunology and Vaccinology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of HealthHost-Pathogen Interactions and Structural Vaccinology Section, Laboratory of Malaria Immunology and Vaccinology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of HealthAbstract 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.https://doi.org/10.1038/s41598-021-85197-3 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Brian Nguyen Rui Ma Wai Kwan Tang Dashuang Shi Niraj H. Tolia |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-03-01 |
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. |
url |
https://doi.org/10.1038/s41598-021-85197-3 |
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