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Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector of Legionella pneumophila

Farnesylation involves covalent linkage of eukaryotic proteins to a lipid moiety to anchor them into membranes, which is essential for the biological function of Ras and other proteins. A large cadre of bacterial effectors is injected into host cells by intravacuolar pathogens through elaborate type...

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Autores principales: Price, Christopher T.D., Al-Quadan, Tasneem, Santic, Marina, Jones, Snake C., Abu Kwaik, Yousef
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916131/
https://www.ncbi.nlm.nih.gov/pubmed/20660614
http://dx.doi.org/10.1084/jem.20100771
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author Price, Christopher T.D.
Al-Quadan, Tasneem
Santic, Marina
Jones, Snake C.
Abu Kwaik, Yousef
author_facet Price, Christopher T.D.
Al-Quadan, Tasneem
Santic, Marina
Jones, Snake C.
Abu Kwaik, Yousef
author_sort Price, Christopher T.D.
collection PubMed
description Farnesylation involves covalent linkage of eukaryotic proteins to a lipid moiety to anchor them into membranes, which is essential for the biological function of Ras and other proteins. A large cadre of bacterial effectors is injected into host cells by intravacuolar pathogens through elaborate type III–VII translocation machineries, and many of these effectors are incorporated into the pathogen-containing vacuolar membrane by unknown mechanisms. The Dot/Icm type IV secretion system of Legionella pneumophila injects into host cells the F-box effector Ankyrin B (AnkB), which functions as platforms for the docking of polyubiquitinated proteins to the Legionella-containing vacuole (LCV) to enable intravacuolar proliferation in macrophages and amoeba. We show that farnesylation of AnkB is indispensable for its anchoring to the cytosolic face of the LCV membrane, for its biological function within macrophages and Dictyostelium discoideum, and for intrapulmonary proliferation in mice. Remarkably, the protein farnesyltransferase, RCE-1 (Ras-converting enzyme-1), and isoprenyl cysteine carboxyl methyltransferase host farnesylation enzymes are recruited to the LCV in a Dot/Icm-dependent manner and are essential for the biological function of AnkB. In conclusion, this study shows novel localized recruitment of the host farnesylation machinery and its anchoring of an F-box effector to the LCV membrane, and this is essential for biological function in vitro and in vivo.
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spelling pubmed-29161312011-02-02 Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector of Legionella pneumophila Price, Christopher T.D. Al-Quadan, Tasneem Santic, Marina Jones, Snake C. Abu Kwaik, Yousef J Exp Med Article Farnesylation involves covalent linkage of eukaryotic proteins to a lipid moiety to anchor them into membranes, which is essential for the biological function of Ras and other proteins. A large cadre of bacterial effectors is injected into host cells by intravacuolar pathogens through elaborate type III–VII translocation machineries, and many of these effectors are incorporated into the pathogen-containing vacuolar membrane by unknown mechanisms. The Dot/Icm type IV secretion system of Legionella pneumophila injects into host cells the F-box effector Ankyrin B (AnkB), which functions as platforms for the docking of polyubiquitinated proteins to the Legionella-containing vacuole (LCV) to enable intravacuolar proliferation in macrophages and amoeba. We show that farnesylation of AnkB is indispensable for its anchoring to the cytosolic face of the LCV membrane, for its biological function within macrophages and Dictyostelium discoideum, and for intrapulmonary proliferation in mice. Remarkably, the protein farnesyltransferase, RCE-1 (Ras-converting enzyme-1), and isoprenyl cysteine carboxyl methyltransferase host farnesylation enzymes are recruited to the LCV in a Dot/Icm-dependent manner and are essential for the biological function of AnkB. In conclusion, this study shows novel localized recruitment of the host farnesylation machinery and its anchoring of an F-box effector to the LCV membrane, and this is essential for biological function in vitro and in vivo. The Rockefeller University Press 2010-08-02 /pmc/articles/PMC2916131/ /pubmed/20660614 http://dx.doi.org/10.1084/jem.20100771 Text en © 2010 Price et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Price, Christopher T.D.
Al-Quadan, Tasneem
Santic, Marina
Jones, Snake C.
Abu Kwaik, Yousef
Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector of Legionella pneumophila
title Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector of Legionella pneumophila
title_full Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector of Legionella pneumophila
title_fullStr Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector of Legionella pneumophila
title_full_unstemmed Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector of Legionella pneumophila
title_short Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector of Legionella pneumophila
title_sort exploitation of conserved eukaryotic host cell farnesylation machinery by an f-box effector of legionella pneumophila
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916131/
https://www.ncbi.nlm.nih.gov/pubmed/20660614
http://dx.doi.org/10.1084/jem.20100771
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