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Measles and Nipah virus assembly: Specific lipid binding drives matrix polymerization
Measles virus, Nipah virus, and multiple other paramyxoviruses cause disease outbreaks in humans and animals worldwide. The paramyxovirus matrix (M) protein mediates virion assembly and budding from host cell membranes. M is thus a key target for antivirals, but few high-resolution structures of par...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299542/ https://www.ncbi.nlm.nih.gov/pubmed/35857835 http://dx.doi.org/10.1126/sciadv.abn1440 |
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author | Norris, Michael J. Husby, Monica L. Kiosses, William B. Yin, Jieyun Saxena, Roopashi Rennick, Linda J. Heiner, Anja Harkins, Stephanie S. Pokhrel, Rudramani Schendel, Sharon L. Hastie, Kathryn M. Landeras-Bueno, Sara Salie, Zhe Li Lee, Benhur Chapagain, Prem P. Maisner, Andrea Duprex, W. Paul Stahelin, Robert V. Saphire, Erica Ollmann |
author_facet | Norris, Michael J. Husby, Monica L. Kiosses, William B. Yin, Jieyun Saxena, Roopashi Rennick, Linda J. Heiner, Anja Harkins, Stephanie S. Pokhrel, Rudramani Schendel, Sharon L. Hastie, Kathryn M. Landeras-Bueno, Sara Salie, Zhe Li Lee, Benhur Chapagain, Prem P. Maisner, Andrea Duprex, W. Paul Stahelin, Robert V. Saphire, Erica Ollmann |
author_sort | Norris, Michael J. |
collection | PubMed |
description | Measles virus, Nipah virus, and multiple other paramyxoviruses cause disease outbreaks in humans and animals worldwide. The paramyxovirus matrix (M) protein mediates virion assembly and budding from host cell membranes. M is thus a key target for antivirals, but few high-resolution structures of paramyxovirus M are available, and we lack the clear understanding of how viral M proteins interact with membrane lipids to mediate viral assembly and egress that is needed to guide antiviral design. Here, we reveal that M proteins associate with phosphatidylserine and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] at the plasma membrane. Using x-ray crystallography, electron microscopy, and molecular dynamics, we demonstrate that PI(4,5)P(2) binding induces conformational and electrostatic changes in the M protein surface that trigger membrane deformation, matrix layer polymerization, and virion assembly. |
format | Online Article Text |
id | pubmed-9299542 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-92995422022-08-09 Measles and Nipah virus assembly: Specific lipid binding drives matrix polymerization Norris, Michael J. Husby, Monica L. Kiosses, William B. Yin, Jieyun Saxena, Roopashi Rennick, Linda J. Heiner, Anja Harkins, Stephanie S. Pokhrel, Rudramani Schendel, Sharon L. Hastie, Kathryn M. Landeras-Bueno, Sara Salie, Zhe Li Lee, Benhur Chapagain, Prem P. Maisner, Andrea Duprex, W. Paul Stahelin, Robert V. Saphire, Erica Ollmann Sci Adv Biomedicine and Life Sciences Measles virus, Nipah virus, and multiple other paramyxoviruses cause disease outbreaks in humans and animals worldwide. The paramyxovirus matrix (M) protein mediates virion assembly and budding from host cell membranes. M is thus a key target for antivirals, but few high-resolution structures of paramyxovirus M are available, and we lack the clear understanding of how viral M proteins interact with membrane lipids to mediate viral assembly and egress that is needed to guide antiviral design. Here, we reveal that M proteins associate with phosphatidylserine and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] at the plasma membrane. Using x-ray crystallography, electron microscopy, and molecular dynamics, we demonstrate that PI(4,5)P(2) binding induces conformational and electrostatic changes in the M protein surface that trigger membrane deformation, matrix layer polymerization, and virion assembly. American Association for the Advancement of Science 2022-07-20 /pmc/articles/PMC9299542/ /pubmed/35857835 http://dx.doi.org/10.1126/sciadv.abn1440 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Norris, Michael J. Husby, Monica L. Kiosses, William B. Yin, Jieyun Saxena, Roopashi Rennick, Linda J. Heiner, Anja Harkins, Stephanie S. Pokhrel, Rudramani Schendel, Sharon L. Hastie, Kathryn M. Landeras-Bueno, Sara Salie, Zhe Li Lee, Benhur Chapagain, Prem P. Maisner, Andrea Duprex, W. Paul Stahelin, Robert V. Saphire, Erica Ollmann Measles and Nipah virus assembly: Specific lipid binding drives matrix polymerization |
title | Measles and Nipah virus assembly: Specific lipid binding drives matrix polymerization |
title_full | Measles and Nipah virus assembly: Specific lipid binding drives matrix polymerization |
title_fullStr | Measles and Nipah virus assembly: Specific lipid binding drives matrix polymerization |
title_full_unstemmed | Measles and Nipah virus assembly: Specific lipid binding drives matrix polymerization |
title_short | Measles and Nipah virus assembly: Specific lipid binding drives matrix polymerization |
title_sort | measles and nipah virus assembly: specific lipid binding drives matrix polymerization |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299542/ https://www.ncbi.nlm.nih.gov/pubmed/35857835 http://dx.doi.org/10.1126/sciadv.abn1440 |
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