Structural and functional studies of the first tripartite protein complex at the Trypanosoma brucei flagellar pocket collar.

The flagellar pocket (FP) is the only endo- and exocytic organelle in most trypanosomes and, as such, is essential throughout the life cycle of the parasite. The neck of the FP is maintained enclosed around the flagellum via the flagellar pocket collar (FPC). The FPC is a macromolecular cytoskeletal...

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Autores principales:	Charlotte Isch, Paul Majneri, Nicolas Landrein, Yulia Pivovarova, Johannes Lesigang, Florian Lauruol, Derrick R Robinson, Gang Dong, Mélanie Bonhivers
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/342552844d3f4eaabbb926a00273446c
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spelling	oai:doaj.org-article:342552844d3f4eaabbb926a00273446c2021-12-02T20:00:27ZStructural and functional studies of the first tripartite protein complex at the Trypanosoma brucei flagellar pocket collar.1553-73661553-737410.1371/journal.ppat.1009329https://doaj.org/article/342552844d3f4eaabbb926a00273446c2021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009329https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The flagellar pocket (FP) is the only endo- and exocytic organelle in most trypanosomes and, as such, is essential throughout the life cycle of the parasite. The neck of the FP is maintained enclosed around the flagellum via the flagellar pocket collar (FPC). The FPC is a macromolecular cytoskeletal structure and is essential for the formation of the FP and cytokinesis. FPC biogenesis and structure are poorly understood, mainly due to the lack of information on FPC composition. To date, only two FPC proteins, BILBO1 and FPC4, have been characterized. BILBO1 forms a molecular skeleton upon which other FPC proteins can, theoretically, dock onto. We previously identified FPC4 as the first BILBO1 interacting partner and demonstrated that its C-terminal domain interacts with the BILBO1 N-terminal domain (NTD). Here, we report by yeast two-hybrid, bioinformatics, functional and structural studies the characterization of a new FPC component and BILBO1 partner protein, BILBO2 (Tb927.6.3240). Further, we demonstrate that BILBO1 and BILBO2 share a homologous NTD and that both domains interact with FPC4. We have determined a 1.9 Å resolution crystal structure of the BILBO2 NTD in complex with the FPC4 BILBO1-binding domain. Together with mutational analyses, our studies reveal key residues for the function of the BILBO2 NTD and its interaction with FPC4 and evidenced a tripartite interaction between BILBO1, BILBO2, and FPC4. Our work sheds light on the first atomic structure of an FPC protein complex and represents a significant step in deciphering the FPC function in Trypanosoma brucei and other pathogenic kinetoplastids.Charlotte IschPaul MajneriNicolas LandreinYulia PivovarovaJohannes LesigangFlorian LauruolDerrick R RobinsonGang DongMélanie BonhiversPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 8, p e1009329 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Charlotte Isch Paul Majneri Nicolas Landrein Yulia Pivovarova Johannes Lesigang Florian Lauruol Derrick R Robinson Gang Dong Mélanie Bonhivers Structural and functional studies of the first tripartite protein complex at the Trypanosoma brucei flagellar pocket collar.
description	The flagellar pocket (FP) is the only endo- and exocytic organelle in most trypanosomes and, as such, is essential throughout the life cycle of the parasite. The neck of the FP is maintained enclosed around the flagellum via the flagellar pocket collar (FPC). The FPC is a macromolecular cytoskeletal structure and is essential for the formation of the FP and cytokinesis. FPC biogenesis and structure are poorly understood, mainly due to the lack of information on FPC composition. To date, only two FPC proteins, BILBO1 and FPC4, have been characterized. BILBO1 forms a molecular skeleton upon which other FPC proteins can, theoretically, dock onto. We previously identified FPC4 as the first BILBO1 interacting partner and demonstrated that its C-terminal domain interacts with the BILBO1 N-terminal domain (NTD). Here, we report by yeast two-hybrid, bioinformatics, functional and structural studies the characterization of a new FPC component and BILBO1 partner protein, BILBO2 (Tb927.6.3240). Further, we demonstrate that BILBO1 and BILBO2 share a homologous NTD and that both domains interact with FPC4. We have determined a 1.9 Å resolution crystal structure of the BILBO2 NTD in complex with the FPC4 BILBO1-binding domain. Together with mutational analyses, our studies reveal key residues for the function of the BILBO2 NTD and its interaction with FPC4 and evidenced a tripartite interaction between BILBO1, BILBO2, and FPC4. Our work sheds light on the first atomic structure of an FPC protein complex and represents a significant step in deciphering the FPC function in Trypanosoma brucei and other pathogenic kinetoplastids.
format	article
author	Charlotte Isch Paul Majneri Nicolas Landrein Yulia Pivovarova Johannes Lesigang Florian Lauruol Derrick R Robinson Gang Dong Mélanie Bonhivers
author_facet	Charlotte Isch Paul Majneri Nicolas Landrein Yulia Pivovarova Johannes Lesigang Florian Lauruol Derrick R Robinson Gang Dong Mélanie Bonhivers
author_sort	Charlotte Isch
title	Structural and functional studies of the first tripartite protein complex at the Trypanosoma brucei flagellar pocket collar.
title_short	Structural and functional studies of the first tripartite protein complex at the Trypanosoma brucei flagellar pocket collar.
title_full	Structural and functional studies of the first tripartite protein complex at the Trypanosoma brucei flagellar pocket collar.
title_fullStr	Structural and functional studies of the first tripartite protein complex at the Trypanosoma brucei flagellar pocket collar.
title_full_unstemmed	Structural and functional studies of the first tripartite protein complex at the Trypanosoma brucei flagellar pocket collar.
title_sort	structural and functional studies of the first tripartite protein complex at the trypanosoma brucei flagellar pocket collar.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/342552844d3f4eaabbb926a00273446c
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Structural and functional studies of the first tripartite protein complex at the Trypanosoma brucei flagellar pocket collar.

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