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Early HIV-1 Gag Assembly on Lipid Membrane with vRNA
HIV-1 capsid assembly is an essential process in the virus infection cycle. Initiation of capsid assembly involves viral proteins, genomic RNA, and the inner leaflet of the plasma membrane, facilitated by a number of cellular factors(1). The viral structural protein Gag plays a number of central rol...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Journal Experts
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350206/ https://www.ncbi.nlm.nih.gov/pubmed/37461524 http://dx.doi.org/10.21203/rs.3.rs-3060076/v1 |
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author | Zhou, Anne X.-Z. Hammond, John A. Sheng, Kai Millar, David P. Williamson, James R. |
author_facet | Zhou, Anne X.-Z. Hammond, John A. Sheng, Kai Millar, David P. Williamson, James R. |
author_sort | Zhou, Anne X.-Z. |
collection | PubMed |
description | HIV-1 capsid assembly is an essential process in the virus infection cycle. Initiation of capsid assembly involves viral proteins, genomic RNA, and the inner leaflet of the plasma membrane, facilitated by a number of cellular factors(1). The viral structural protein Gag plays a number of central roles in this process, including association with the membrane, selective binding of genomic RNA, and oligomerization and packaging to ultimately produce an immature budded pro-viral particle(2). While there have been intensive studies regarding the early stages of Gag assembly, there is a lack of consensus on the mechanism for nucleation and growth of Gag complexes(3–7). Here we show that myristoylated Gag forms a trimer nucleus in a model membrane that can selectively bind a dimeric RNA containing the packaging signal. Subsequent growth of myristoyl-Gag oligomers requires vRNA, and occurs by addition of 1 or 2 Gag monomers at a time from solution. These data support a model where the immature capsid lattice formation occurs by a gradual lattice edge expansion, following a trimeric nucleation event. The dynamic single molecule data that support this model were recorded using mass photometry, involving full length myristoylated protein, RNA, and lipid together. These data are the first to support a lattice edge expansion model of Gag during early stages of assembly in a biological-relevant setting, providing insights to the fundamental models of virus structural protein assembly process. |
format | Online Article Text |
id | pubmed-10350206 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Journal Experts |
record_format | MEDLINE/PubMed |
spelling | pubmed-103502062023-07-17 Early HIV-1 Gag Assembly on Lipid Membrane with vRNA Zhou, Anne X.-Z. Hammond, John A. Sheng, Kai Millar, David P. Williamson, James R. Res Sq Article HIV-1 capsid assembly is an essential process in the virus infection cycle. Initiation of capsid assembly involves viral proteins, genomic RNA, and the inner leaflet of the plasma membrane, facilitated by a number of cellular factors(1). The viral structural protein Gag plays a number of central roles in this process, including association with the membrane, selective binding of genomic RNA, and oligomerization and packaging to ultimately produce an immature budded pro-viral particle(2). While there have been intensive studies regarding the early stages of Gag assembly, there is a lack of consensus on the mechanism for nucleation and growth of Gag complexes(3–7). Here we show that myristoylated Gag forms a trimer nucleus in a model membrane that can selectively bind a dimeric RNA containing the packaging signal. Subsequent growth of myristoyl-Gag oligomers requires vRNA, and occurs by addition of 1 or 2 Gag monomers at a time from solution. These data support a model where the immature capsid lattice formation occurs by a gradual lattice edge expansion, following a trimeric nucleation event. The dynamic single molecule data that support this model were recorded using mass photometry, involving full length myristoylated protein, RNA, and lipid together. These data are the first to support a lattice edge expansion model of Gag during early stages of assembly in a biological-relevant setting, providing insights to the fundamental models of virus structural protein assembly process. American Journal Experts 2023-07-03 /pmc/articles/PMC10350206/ /pubmed/37461524 http://dx.doi.org/10.21203/rs.3.rs-3060076/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Zhou, Anne X.-Z. Hammond, John A. Sheng, Kai Millar, David P. Williamson, James R. Early HIV-1 Gag Assembly on Lipid Membrane with vRNA |
title | Early HIV-1 Gag Assembly on Lipid Membrane with vRNA |
title_full | Early HIV-1 Gag Assembly on Lipid Membrane with vRNA |
title_fullStr | Early HIV-1 Gag Assembly on Lipid Membrane with vRNA |
title_full_unstemmed | Early HIV-1 Gag Assembly on Lipid Membrane with vRNA |
title_short | Early HIV-1 Gag Assembly on Lipid Membrane with vRNA |
title_sort | early hiv-1 gag assembly on lipid membrane with vrna |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350206/ https://www.ncbi.nlm.nih.gov/pubmed/37461524 http://dx.doi.org/10.21203/rs.3.rs-3060076/v1 |
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