Direct binding to GABARAP family members is essential for HIV-1 Nef plasma membrane localization

Abstract HIV-1 Nef is an important pathogenic factor for HIV/AIDS pathogenesis. Studies have shown that the association of Nef with the inner leaflet of the plasma membrane and with endocytic and perinuclear vesicles is essential for most activities of Nef. Using purified recombinant proteins in pul...

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Autores principales: Alexandra Boeske, Melanie Schwarten, Peixiang Ma, Markus Tusche, Jessica Mötter, Christina Möller, Philipp Neudecker, Silke Hoffmann, Dieter Willbold
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/03e0e78ce7bf4b4b9c679247f861c77c
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spelling oai:doaj.org-article:03e0e78ce7bf4b4b9c679247f861c77c2021-12-02T15:05:04ZDirect binding to GABARAP family members is essential for HIV-1 Nef plasma membrane localization10.1038/s41598-017-06319-42045-2322https://doaj.org/article/03e0e78ce7bf4b4b9c679247f861c77c2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06319-4https://doaj.org/toc/2045-2322Abstract HIV-1 Nef is an important pathogenic factor for HIV/AIDS pathogenesis. Studies have shown that the association of Nef with the inner leaflet of the plasma membrane and with endocytic and perinuclear vesicles is essential for most activities of Nef. Using purified recombinant proteins in pull-down assays and by co-immunoprecipitation assays we demonstrate that Nef binds directly and specifically to all GABARAP family members, but not to LC3 family members. Based on nuclear magnetic resonance (NMR) experiments we showed that Nef binds to GABARAP via two surface exposed hydrophobic pockets. S53 and F62 of GABARAP were identified as key residues for the interaction with Nef. During live-cell fluorescence microscopy an accumulation of Nef and all GABARAP family members in vesicular structures throughout the cytoplasm and at the plasma membrane was observed. This plasma membrane accumulation was significantly reduced after knocking down GABARAP, GABARAPL1 and GABARAPL2 with respective siRNAs. We identified GABARAPs as the first known direct interaction partners of Nef that are essential for its plasma membrane localization.Alexandra BoeskeMelanie SchwartenPeixiang MaMarkus TuscheJessica MötterChristina MöllerPhilipp NeudeckerSilke HoffmannDieter WillboldNature 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
Alexandra Boeske
Melanie Schwarten
Peixiang Ma
Markus Tusche
Jessica Mötter
Christina Möller
Philipp Neudecker
Silke Hoffmann
Dieter Willbold
Direct binding to GABARAP family members is essential for HIV-1 Nef plasma membrane localization
description Abstract HIV-1 Nef is an important pathogenic factor for HIV/AIDS pathogenesis. Studies have shown that the association of Nef with the inner leaflet of the plasma membrane and with endocytic and perinuclear vesicles is essential for most activities of Nef. Using purified recombinant proteins in pull-down assays and by co-immunoprecipitation assays we demonstrate that Nef binds directly and specifically to all GABARAP family members, but not to LC3 family members. Based on nuclear magnetic resonance (NMR) experiments we showed that Nef binds to GABARAP via two surface exposed hydrophobic pockets. S53 and F62 of GABARAP were identified as key residues for the interaction with Nef. During live-cell fluorescence microscopy an accumulation of Nef and all GABARAP family members in vesicular structures throughout the cytoplasm and at the plasma membrane was observed. This plasma membrane accumulation was significantly reduced after knocking down GABARAP, GABARAPL1 and GABARAPL2 with respective siRNAs. We identified GABARAPs as the first known direct interaction partners of Nef that are essential for its plasma membrane localization.
format article
author Alexandra Boeske
Melanie Schwarten
Peixiang Ma
Markus Tusche
Jessica Mötter
Christina Möller
Philipp Neudecker
Silke Hoffmann
Dieter Willbold
author_facet Alexandra Boeske
Melanie Schwarten
Peixiang Ma
Markus Tusche
Jessica Mötter
Christina Möller
Philipp Neudecker
Silke Hoffmann
Dieter Willbold
author_sort Alexandra Boeske
title Direct binding to GABARAP family members is essential for HIV-1 Nef plasma membrane localization
title_short Direct binding to GABARAP family members is essential for HIV-1 Nef plasma membrane localization
title_full Direct binding to GABARAP family members is essential for HIV-1 Nef plasma membrane localization
title_fullStr Direct binding to GABARAP family members is essential for HIV-1 Nef plasma membrane localization
title_full_unstemmed Direct binding to GABARAP family members is essential for HIV-1 Nef plasma membrane localization
title_sort direct binding to gabarap family members is essential for hiv-1 nef plasma membrane localization
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/03e0e78ce7bf4b4b9c679247f861c77c
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