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Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1
BST2/tetherin, an antiviral restriction factor, inhibits the release of enveloped viruses from the cell surface. Human immunodeficiency virus-1 (HIV-1) antagonizes BST2 through viral protein u (Vpu), which downregulates BST2 from the cell surface. We report the crystal structure of a protein complex...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018625/ https://www.ncbi.nlm.nih.gov/pubmed/24843023 http://dx.doi.org/10.7554/eLife.02362 |
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author | Jia, Xiaofei Weber, Erin Tokarev, Andrey Lewinski, Mary Rizk, Maryan Suarez, Marissa Guatelli, John Xiong, Yong |
author_facet | Jia, Xiaofei Weber, Erin Tokarev, Andrey Lewinski, Mary Rizk, Maryan Suarez, Marissa Guatelli, John Xiong, Yong |
author_sort | Jia, Xiaofei |
collection | PubMed |
description | BST2/tetherin, an antiviral restriction factor, inhibits the release of enveloped viruses from the cell surface. Human immunodeficiency virus-1 (HIV-1) antagonizes BST2 through viral protein u (Vpu), which downregulates BST2 from the cell surface. We report the crystal structure of a protein complex containing Vpu and BST2 cytoplasmic domains and the core of the clathrin adaptor protein complex 1 (AP1). This, together with our biochemical and functional validations, reveals how Vpu hijacks the AP1-dependent membrane trafficking pathways to mistraffick BST2. Vpu mimics a canonical acidic dileucine-sorting motif to bind AP1 in the cytosol, while simultaneously interacting with BST2 in the membrane. These interactions enable Vpu to build on an intrinsic interaction between BST2 and AP1, presumably causing the observed retention of BST2 in juxtanuclear endosomes and stimulating its degradation in lysosomes. The ability of Vpu to hijack AP-dependent trafficking pathways suggests a potential common theme for Vpu-mediated downregulation of host proteins. DOI: http://dx.doi.org/10.7554/eLife.02362.001 |
format | Online Article Text |
id | pubmed-4018625 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-40186252014-05-22 Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1 Jia, Xiaofei Weber, Erin Tokarev, Andrey Lewinski, Mary Rizk, Maryan Suarez, Marissa Guatelli, John Xiong, Yong eLife Biophysics and Structural Biology BST2/tetherin, an antiviral restriction factor, inhibits the release of enveloped viruses from the cell surface. Human immunodeficiency virus-1 (HIV-1) antagonizes BST2 through viral protein u (Vpu), which downregulates BST2 from the cell surface. We report the crystal structure of a protein complex containing Vpu and BST2 cytoplasmic domains and the core of the clathrin adaptor protein complex 1 (AP1). This, together with our biochemical and functional validations, reveals how Vpu hijacks the AP1-dependent membrane trafficking pathways to mistraffick BST2. Vpu mimics a canonical acidic dileucine-sorting motif to bind AP1 in the cytosol, while simultaneously interacting with BST2 in the membrane. These interactions enable Vpu to build on an intrinsic interaction between BST2 and AP1, presumably causing the observed retention of BST2 in juxtanuclear endosomes and stimulating its degradation in lysosomes. The ability of Vpu to hijack AP-dependent trafficking pathways suggests a potential common theme for Vpu-mediated downregulation of host proteins. DOI: http://dx.doi.org/10.7554/eLife.02362.001 eLife Sciences Publications, Ltd 2014-04-29 /pmc/articles/PMC4018625/ /pubmed/24843023 http://dx.doi.org/10.7554/eLife.02362 Text en Copyright © 2014, Jia et al http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biophysics and Structural Biology Jia, Xiaofei Weber, Erin Tokarev, Andrey Lewinski, Mary Rizk, Maryan Suarez, Marissa Guatelli, John Xiong, Yong Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1 |
title | Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1 |
title_full | Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1 |
title_fullStr | Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1 |
title_full_unstemmed | Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1 |
title_short | Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1 |
title_sort | structural basis of hiv-1 vpu-mediated bst2 antagonism via hijacking of the clathrin adaptor protein complex 1 |
topic | Biophysics and Structural Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018625/ https://www.ncbi.nlm.nih.gov/pubmed/24843023 http://dx.doi.org/10.7554/eLife.02362 |
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