Cholesterol in the Viral Membrane is a Molecular Switch Governing HIV‐1 Env Clustering
Abstract HIV‐1 entry requires the redistribution of envelope glycoproteins (Env) into a cluster and the presence of cholesterol (chol) in the viral membrane. However, the molecular mechanisms underlying the specific role of chol in infectivity and the driving force behind Env clustering remain unkno...
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doaj-6f4e93d03c3e45a59350ab5ec6a292922021-02-03T12:50:59ZengWileyAdvanced Science2198-38442021-02-0183n/an/a10.1002/advs.202003468Cholesterol in the Viral Membrane is a Molecular Switch Governing HIV‐1 Env ClusteringJon Ander Nieto‐Garai0Aroa Arboleya1Sara Otaegi2Jakub Chojnacki3Josefina Casas4Gemma Fabriàs5F‐Xabier Contreras6Hans‐Georg Kräusslich7Maier Lorizate8Instituto Biofisika (UPV/EHU, CSIC) University of the Basque Country Leioa E‐48940 SpainInstituto Biofisika (UPV/EHU, CSIC) University of the Basque Country Leioa E‐48940 SpainInstituto Biofisika (UPV/EHU, CSIC) University of the Basque Country Leioa E‐48940 SpainIrsiCaixa AIDS Research Institute Badalona 08916 SpainResearch Unit on BioActive Molecules. Department of Biological Chemistry Institute for Advanced Chemistry of Catalonia (IQAC‐CSIC) Barcelona Catalonia 08034 SpainResearch Unit on BioActive Molecules. Department of Biological Chemistry Institute for Advanced Chemistry of Catalonia (IQAC‐CSIC) Barcelona Catalonia 08034 SpainInstituto Biofisika (UPV/EHU, CSIC) University of the Basque Country Leioa E‐48940 SpainDepartment of Infectious Diseases Virology Universitätsklinikum Heidelberg Heidelberg 69120 GermanyInstituto Biofisika (UPV/EHU, CSIC) University of the Basque Country Leioa E‐48940 SpainAbstract HIV‐1 entry requires the redistribution of envelope glycoproteins (Env) into a cluster and the presence of cholesterol (chol) in the viral membrane. However, the molecular mechanisms underlying the specific role of chol in infectivity and the driving force behind Env clustering remain unknown. Here, gp41 is demonstrated to directly interact with chol in the viral membrane via residues 751–854 in the cytoplasmic tail (CT751–854). Super‐resolution stimulated emission depletion (STED) nanoscopy analysis of Env distribution further demonstrates that both truncation of gp41 CT751–854 and depletion of chol leads to dispersion of Env clusters in the viral membrane and inhibition of virus entry. This work reveals a direct interaction of gp41 CT with chol and indicates that this interaction is an important orchestrator of Env clustering.https://doi.org/10.1002/advs.202003468cholesterolEnv clusteringgp41 cytoplasmic tailsHIV‐1protein–lipid interactions |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jon Ander Nieto‐Garai Aroa Arboleya Sara Otaegi Jakub Chojnacki Josefina Casas Gemma Fabriàs F‐Xabier Contreras Hans‐Georg Kräusslich Maier Lorizate |
spellingShingle |
Jon Ander Nieto‐Garai Aroa Arboleya Sara Otaegi Jakub Chojnacki Josefina Casas Gemma Fabriàs F‐Xabier Contreras Hans‐Georg Kräusslich Maier Lorizate Cholesterol in the Viral Membrane is a Molecular Switch Governing HIV‐1 Env Clustering Advanced Science cholesterol Env clustering gp41 cytoplasmic tails HIV‐1 protein–lipid interactions |
author_facet |
Jon Ander Nieto‐Garai Aroa Arboleya Sara Otaegi Jakub Chojnacki Josefina Casas Gemma Fabriàs F‐Xabier Contreras Hans‐Georg Kräusslich Maier Lorizate |
author_sort |
Jon Ander Nieto‐Garai |
title |
Cholesterol in the Viral Membrane is a Molecular Switch Governing HIV‐1 Env Clustering |
title_short |
Cholesterol in the Viral Membrane is a Molecular Switch Governing HIV‐1 Env Clustering |
title_full |
Cholesterol in the Viral Membrane is a Molecular Switch Governing HIV‐1 Env Clustering |
title_fullStr |
Cholesterol in the Viral Membrane is a Molecular Switch Governing HIV‐1 Env Clustering |
title_full_unstemmed |
Cholesterol in the Viral Membrane is a Molecular Switch Governing HIV‐1 Env Clustering |
title_sort |
cholesterol in the viral membrane is a molecular switch governing hiv‐1 env clustering |
publisher |
Wiley |
series |
Advanced Science |
issn |
2198-3844 |
publishDate |
2021-02-01 |
description |
Abstract HIV‐1 entry requires the redistribution of envelope glycoproteins (Env) into a cluster and the presence of cholesterol (chol) in the viral membrane. However, the molecular mechanisms underlying the specific role of chol in infectivity and the driving force behind Env clustering remain unknown. Here, gp41 is demonstrated to directly interact with chol in the viral membrane via residues 751–854 in the cytoplasmic tail (CT751–854). Super‐resolution stimulated emission depletion (STED) nanoscopy analysis of Env distribution further demonstrates that both truncation of gp41 CT751–854 and depletion of chol leads to dispersion of Env clusters in the viral membrane and inhibition of virus entry. This work reveals a direct interaction of gp41 CT with chol and indicates that this interaction is an important orchestrator of Env clustering. |
topic |
cholesterol Env clustering gp41 cytoplasmic tails HIV‐1 protein–lipid interactions |
url |
https://doi.org/10.1002/advs.202003468 |
work_keys_str_mv |
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