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Tsg101 chaperone function revealed by HIV-1 assembly inhibitors
HIV-1 replication requires Tsg101, a component of cellular endosomal sorting complex required for transport (ESCRT) machinery. Tsg101 possesses an ubiquitin (Ub) E2 variant (UEV) domain with a pocket that can bind PT/SAP motifs and another pocket that can bind Ub. The PTAP motif in the viral structu...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680296/ https://www.ncbi.nlm.nih.gov/pubmed/29123089 http://dx.doi.org/10.1038/s41467-017-01426-2 |
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author | Strickland, Madeleine Ehrlich, Lorna S. Watanabe, Susan Khan, Mahfuz Strub, Marie-Paule Luan, Chi-Hao Powell, Michael D. Leis, Jonathan Tjandra, Nico Carter, Carol A. |
author_facet | Strickland, Madeleine Ehrlich, Lorna S. Watanabe, Susan Khan, Mahfuz Strub, Marie-Paule Luan, Chi-Hao Powell, Michael D. Leis, Jonathan Tjandra, Nico Carter, Carol A. |
author_sort | Strickland, Madeleine |
collection | PubMed |
description | HIV-1 replication requires Tsg101, a component of cellular endosomal sorting complex required for transport (ESCRT) machinery. Tsg101 possesses an ubiquitin (Ub) E2 variant (UEV) domain with a pocket that can bind PT/SAP motifs and another pocket that can bind Ub. The PTAP motif in the viral structural precursor polyprotein, Gag, allows the recruitment of Tsg101 and other ESCRTs to virus assembly sites where they mediate budding. It is not known how or even whether the UEV Ub binding function contributes to virus production. Here, we report that disruption of UEV Ub binding by commonly used drugs arrests assembly at an early step distinct from the late stage involving PTAP binding disruption. NMR reveals that the drugs form a covalent adduct near the Ub-binding pocket leading to the disruption of Ub, but not PTAP binding. We conclude that the Ub-binding pocket has a chaperone function involved in bud initiation. |
format | Online Article Text |
id | pubmed-5680296 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56802962017-11-15 Tsg101 chaperone function revealed by HIV-1 assembly inhibitors Strickland, Madeleine Ehrlich, Lorna S. Watanabe, Susan Khan, Mahfuz Strub, Marie-Paule Luan, Chi-Hao Powell, Michael D. Leis, Jonathan Tjandra, Nico Carter, Carol A. Nat Commun Article HIV-1 replication requires Tsg101, a component of cellular endosomal sorting complex required for transport (ESCRT) machinery. Tsg101 possesses an ubiquitin (Ub) E2 variant (UEV) domain with a pocket that can bind PT/SAP motifs and another pocket that can bind Ub. The PTAP motif in the viral structural precursor polyprotein, Gag, allows the recruitment of Tsg101 and other ESCRTs to virus assembly sites where they mediate budding. It is not known how or even whether the UEV Ub binding function contributes to virus production. Here, we report that disruption of UEV Ub binding by commonly used drugs arrests assembly at an early step distinct from the late stage involving PTAP binding disruption. NMR reveals that the drugs form a covalent adduct near the Ub-binding pocket leading to the disruption of Ub, but not PTAP binding. We conclude that the Ub-binding pocket has a chaperone function involved in bud initiation. Nature Publishing Group UK 2017-11-09 /pmc/articles/PMC5680296/ /pubmed/29123089 http://dx.doi.org/10.1038/s41467-017-01426-2 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Strickland, Madeleine Ehrlich, Lorna S. Watanabe, Susan Khan, Mahfuz Strub, Marie-Paule Luan, Chi-Hao Powell, Michael D. Leis, Jonathan Tjandra, Nico Carter, Carol A. Tsg101 chaperone function revealed by HIV-1 assembly inhibitors |
title | Tsg101 chaperone function revealed by HIV-1 assembly inhibitors |
title_full | Tsg101 chaperone function revealed by HIV-1 assembly inhibitors |
title_fullStr | Tsg101 chaperone function revealed by HIV-1 assembly inhibitors |
title_full_unstemmed | Tsg101 chaperone function revealed by HIV-1 assembly inhibitors |
title_short | Tsg101 chaperone function revealed by HIV-1 assembly inhibitors |
title_sort | tsg101 chaperone function revealed by hiv-1 assembly inhibitors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680296/ https://www.ncbi.nlm.nih.gov/pubmed/29123089 http://dx.doi.org/10.1038/s41467-017-01426-2 |
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