Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei

Abstract Trypanosoma brucei is a unicellular parasite responsible for African trypanosomiasis or sleeping sickness. It contains a single PARP enzyme opposed to many higher eukaryotes, which have numerous PARPs. PARPs are responsible for a post-translational modification, ADP-ribosylation, regulating...

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Autores principales:	Teemu Haikarainen, Mariana Schlesinger, Ezeogo Obaji, Silvia H. Fernández Villamil, Lari Lehtiö
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/383567bfb60a4e1f9f36829cf9b4a8ca
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spelling	oai:doaj.org-article:383567bfb60a4e1f9f36829cf9b4a8ca2021-12-02T11:52:56ZStructural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei10.1038/s41598-017-03751-42045-2322https://doaj.org/article/383567bfb60a4e1f9f36829cf9b4a8ca2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03751-4https://doaj.org/toc/2045-2322Abstract Trypanosoma brucei is a unicellular parasite responsible for African trypanosomiasis or sleeping sickness. It contains a single PARP enzyme opposed to many higher eukaryotes, which have numerous PARPs. PARPs are responsible for a post-translational modification, ADP-ribosylation, regulating a multitude of cellular events. T. brucei PARP, like human PARPs-1-3, is activated by DNA binding and it potentially functions in DNA repair processes. Here we characterized activation requirements, structure and subcellular localization of T. brucei PARP. T. brucei PARP was found to be selectively activated by 5′ phosphorylated and 3′ phosphorylated DNA breaks. Importantly, the N-terminal region is responsible for high-affinity DNA-binding and required for DNA-dependent enzymatic activation. This module is also required for nuclear localization of the protein in response to oxidative stress. Solution structures of activating and non-activating PARP-DNA complexes were determined with small-angle X-ray scattering revealing distinct differences in their DNA-binding modes.Teemu HaikarainenMariana SchlesingerEzeogo ObajiSilvia H. Fernández VillamilLari LehtiöNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Teemu Haikarainen Mariana Schlesinger Ezeogo Obaji Silvia H. Fernández Villamil Lari Lehtiö Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei
description	Abstract Trypanosoma brucei is a unicellular parasite responsible for African trypanosomiasis or sleeping sickness. It contains a single PARP enzyme opposed to many higher eukaryotes, which have numerous PARPs. PARPs are responsible for a post-translational modification, ADP-ribosylation, regulating a multitude of cellular events. T. brucei PARP, like human PARPs-1-3, is activated by DNA binding and it potentially functions in DNA repair processes. Here we characterized activation requirements, structure and subcellular localization of T. brucei PARP. T. brucei PARP was found to be selectively activated by 5′ phosphorylated and 3′ phosphorylated DNA breaks. Importantly, the N-terminal region is responsible for high-affinity DNA-binding and required for DNA-dependent enzymatic activation. This module is also required for nuclear localization of the protein in response to oxidative stress. Solution structures of activating and non-activating PARP-DNA complexes were determined with small-angle X-ray scattering revealing distinct differences in their DNA-binding modes.
format	article
author	Teemu Haikarainen Mariana Schlesinger Ezeogo Obaji Silvia H. Fernández Villamil Lari Lehtiö
author_facet	Teemu Haikarainen Mariana Schlesinger Ezeogo Obaji Silvia H. Fernández Villamil Lari Lehtiö
author_sort	Teemu Haikarainen
title	Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei
title_short	Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei
title_full	Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei
title_fullStr	Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei
title_full_unstemmed	Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei
title_sort	structural and biochemical characterization of poly-adp-ribose polymerase from trypanosoma brucei
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/383567bfb60a4e1f9f36829cf9b4a8ca
work_keys_str_mv	AT teemuhaikarainen structuralandbiochemicalcharacterizationofpolyadpribosepolymerasefromtrypanosomabrucei AT marianaschlesinger structuralandbiochemicalcharacterizationofpolyadpribosepolymerasefromtrypanosomabrucei AT ezeogoobaji structuralandbiochemicalcharacterizationofpolyadpribosepolymerasefromtrypanosomabrucei AT silviahfernandezvillamil structuralandbiochemicalcharacterizationofpolyadpribosepolymerasefromtrypanosomabrucei AT larilehtio structuralandbiochemicalcharacterizationofpolyadpribosepolymerasefromtrypanosomabrucei
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Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei

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