Nanobody-mediated macromolecular crowding induces membrane fission and remodeling in the African trypanosome

Summary: The dense variant surface glycoprotein (VSG) coat of African trypanosomes represents the primary host-pathogen interface. Antigenic variation prevents clearing of the pathogen by employing a large repertoire of antigenically distinct VSG genes, thus neutralizing the host’s antibody response...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Alexander Hempelmann, Laura Hartleb, Monique van Straaten, Hamidreza Hashemi, Johan P. Zeelen, Kevin Bongers, F. Nina Papavasiliou, Markus Engstler, C. Erec Stebbins, Nicola G. Jones
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	African trypanosome host-pathogen interaction variant surface glycoproteins immune epitope mapping structural biology nanovesicle formation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c3acb4d7657a4e0b8cad190d14971cdf
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c3acb4d7657a4e0b8cad190d14971cdf
record_format	dspace
spelling	oai:doaj.org-article:c3acb4d7657a4e0b8cad190d14971cdf2021-11-04T04:29:11ZNanobody-mediated macromolecular crowding induces membrane fission and remodeling in the African trypanosome2211-124710.1016/j.celrep.2021.109923https://doaj.org/article/c3acb4d7657a4e0b8cad190d14971cdf2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721013966https://doaj.org/toc/2211-1247Summary: The dense variant surface glycoprotein (VSG) coat of African trypanosomes represents the primary host-pathogen interface. Antigenic variation prevents clearing of the pathogen by employing a large repertoire of antigenically distinct VSG genes, thus neutralizing the host’s antibody response. To explore the epitope space of VSGs, we generate anti-VSG nanobodies and combine high-resolution structural analysis of VSG-nanobody complexes with binding assays on living cells, revealing that these camelid antibodies bind deeply inside the coat. One nanobody causes rapid loss of cellular motility, possibly due to blockage of VSG mobility on the coat, whose rapid endocytosis and exocytosis are mechanistically linked to Trypanosoma brucei propulsion and whose density is required for survival. Electron microscopy studies demonstrate that this loss of motility is accompanied by rapid formation and shedding of nanovesicles and nanotubes, suggesting that increased protein crowding on the dense membrane can be a driving force for membrane fission in living cells.Alexander HempelmannLaura HartlebMonique van StraatenHamidreza HashemiJohan P. ZeelenKevin BongersF. Nina PapavasiliouMarkus EngstlerC. Erec StebbinsNicola G. JonesElsevierarticleAfrican trypanosomehost-pathogen interactionvariant surface glycoproteinsimmune epitope mappingstructural biologynanovesicle formationBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109923- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	African trypanosome host-pathogen interaction variant surface glycoproteins immune epitope mapping structural biology nanovesicle formation Biology (General) QH301-705.5
spellingShingle	African trypanosome host-pathogen interaction variant surface glycoproteins immune epitope mapping structural biology nanovesicle formation Biology (General) QH301-705.5 Alexander Hempelmann Laura Hartleb Monique van Straaten Hamidreza Hashemi Johan P. Zeelen Kevin Bongers F. Nina Papavasiliou Markus Engstler C. Erec Stebbins Nicola G. Jones Nanobody-mediated macromolecular crowding induces membrane fission and remodeling in the African trypanosome
description	Summary: The dense variant surface glycoprotein (VSG) coat of African trypanosomes represents the primary host-pathogen interface. Antigenic variation prevents clearing of the pathogen by employing a large repertoire of antigenically distinct VSG genes, thus neutralizing the host’s antibody response. To explore the epitope space of VSGs, we generate anti-VSG nanobodies and combine high-resolution structural analysis of VSG-nanobody complexes with binding assays on living cells, revealing that these camelid antibodies bind deeply inside the coat. One nanobody causes rapid loss of cellular motility, possibly due to blockage of VSG mobility on the coat, whose rapid endocytosis and exocytosis are mechanistically linked to Trypanosoma brucei propulsion and whose density is required for survival. Electron microscopy studies demonstrate that this loss of motility is accompanied by rapid formation and shedding of nanovesicles and nanotubes, suggesting that increased protein crowding on the dense membrane can be a driving force for membrane fission in living cells.
format	article
author	Alexander Hempelmann Laura Hartleb Monique van Straaten Hamidreza Hashemi Johan P. Zeelen Kevin Bongers F. Nina Papavasiliou Markus Engstler C. Erec Stebbins Nicola G. Jones
author_facet	Alexander Hempelmann Laura Hartleb Monique van Straaten Hamidreza Hashemi Johan P. Zeelen Kevin Bongers F. Nina Papavasiliou Markus Engstler C. Erec Stebbins Nicola G. Jones
author_sort	Alexander Hempelmann
title	Nanobody-mediated macromolecular crowding induces membrane fission and remodeling in the African trypanosome
title_short	Nanobody-mediated macromolecular crowding induces membrane fission and remodeling in the African trypanosome
title_full	Nanobody-mediated macromolecular crowding induces membrane fission and remodeling in the African trypanosome
title_fullStr	Nanobody-mediated macromolecular crowding induces membrane fission and remodeling in the African trypanosome
title_full_unstemmed	Nanobody-mediated macromolecular crowding induces membrane fission and remodeling in the African trypanosome
title_sort	nanobody-mediated macromolecular crowding induces membrane fission and remodeling in the african trypanosome
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/c3acb4d7657a4e0b8cad190d14971cdf
work_keys_str_mv	AT alexanderhempelmann nanobodymediatedmacromolecularcrowdinginducesmembranefissionandremodelingintheafricantrypanosome AT laurahartleb nanobodymediatedmacromolecularcrowdinginducesmembranefissionandremodelingintheafricantrypanosome AT moniquevanstraaten nanobodymediatedmacromolecularcrowdinginducesmembranefissionandremodelingintheafricantrypanosome AT hamidrezahashemi nanobodymediatedmacromolecularcrowdinginducesmembranefissionandremodelingintheafricantrypanosome AT johanpzeelen nanobodymediatedmacromolecularcrowdinginducesmembranefissionandremodelingintheafricantrypanosome AT kevinbongers nanobodymediatedmacromolecularcrowdinginducesmembranefissionandremodelingintheafricantrypanosome AT fninapapavasiliou nanobodymediatedmacromolecularcrowdinginducesmembranefissionandremodelingintheafricantrypanosome AT markusengstler nanobodymediatedmacromolecularcrowdinginducesmembranefissionandremodelingintheafricantrypanosome AT cerecstebbins nanobodymediatedmacromolecularcrowdinginducesmembranefissionandremodelingintheafricantrypanosome AT nicolagjones nanobodymediatedmacromolecularcrowdinginducesmembranefissionandremodelingintheafricantrypanosome
_version_	1718445299761938432

Nanobody-mediated macromolecular crowding induces membrane fission and remodeling in the African trypanosome

Ejemplares similares