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Structural Analysis of HIV-1 Maturation Using Cryo-Electron Tomography

HIV-1 buds form infected cells in an immature, non-infectious form. Maturation into an infectious virion requires proteolytic cleavage of the Gag polyprotein at five positions, leading to a dramatic change in virus morphology. Immature virions contain an incomplete spherical shell where Gag is arran...

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Autores principales: de Marco, Alex, Müller, Barbara, Glass, Bärbel, Riches, James D., Kräusslich, Hans-Georg, Briggs, John A. G.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999899/
https://www.ncbi.nlm.nih.gov/pubmed/21151640
http://dx.doi.org/10.1371/journal.ppat.1001215
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author de Marco, Alex
Müller, Barbara
Glass, Bärbel
Riches, James D.
Kräusslich, Hans-Georg
Briggs, John A. G.
author_facet de Marco, Alex
Müller, Barbara
Glass, Bärbel
Riches, James D.
Kräusslich, Hans-Georg
Briggs, John A. G.
author_sort de Marco, Alex
collection PubMed
description HIV-1 buds form infected cells in an immature, non-infectious form. Maturation into an infectious virion requires proteolytic cleavage of the Gag polyprotein at five positions, leading to a dramatic change in virus morphology. Immature virions contain an incomplete spherical shell where Gag is arranged with the N-terminal MA domain adjacent to the membrane, the CA domain adopting a hexameric lattice below the membrane, and beneath this, the NC domain and viral RNA forming a disordered layer. After maturation, NC and RNA are condensed within the particle surrounded by a conical CA core. Little is known about the sequence of structural changes that take place during maturation, however. Here we have used cryo-electron tomography and subtomogram averaging to resolve the structure of the Gag lattice in a panel of viruses containing point mutations abolishing cleavage at individual or multiple Gag cleavage sites. These studies describe the structural intermediates correlating with the ordered processing events that occur during the HIV-1 maturation process. After the first cleavage between SP1 and NC, the condensed NC-RNA may retain a link to the remaining Gag lattice. Initiation of disassembly of the immature Gag lattice requires cleavage to occur on both sides of CA-SP1, while assembly of the mature core also requires cleavage of SP1 from CA.
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spelling pubmed-29998992010-12-13 Structural Analysis of HIV-1 Maturation Using Cryo-Electron Tomography de Marco, Alex Müller, Barbara Glass, Bärbel Riches, James D. Kräusslich, Hans-Georg Briggs, John A. G. PLoS Pathog Research Article HIV-1 buds form infected cells in an immature, non-infectious form. Maturation into an infectious virion requires proteolytic cleavage of the Gag polyprotein at five positions, leading to a dramatic change in virus morphology. Immature virions contain an incomplete spherical shell where Gag is arranged with the N-terminal MA domain adjacent to the membrane, the CA domain adopting a hexameric lattice below the membrane, and beneath this, the NC domain and viral RNA forming a disordered layer. After maturation, NC and RNA are condensed within the particle surrounded by a conical CA core. Little is known about the sequence of structural changes that take place during maturation, however. Here we have used cryo-electron tomography and subtomogram averaging to resolve the structure of the Gag lattice in a panel of viruses containing point mutations abolishing cleavage at individual or multiple Gag cleavage sites. These studies describe the structural intermediates correlating with the ordered processing events that occur during the HIV-1 maturation process. After the first cleavage between SP1 and NC, the condensed NC-RNA may retain a link to the remaining Gag lattice. Initiation of disassembly of the immature Gag lattice requires cleavage to occur on both sides of CA-SP1, while assembly of the mature core also requires cleavage of SP1 from CA. Public Library of Science 2010-11-24 /pmc/articles/PMC2999899/ /pubmed/21151640 http://dx.doi.org/10.1371/journal.ppat.1001215 Text en de Marco et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
de Marco, Alex
Müller, Barbara
Glass, Bärbel
Riches, James D.
Kräusslich, Hans-Georg
Briggs, John A. G.
Structural Analysis of HIV-1 Maturation Using Cryo-Electron Tomography
title Structural Analysis of HIV-1 Maturation Using Cryo-Electron Tomography
title_full Structural Analysis of HIV-1 Maturation Using Cryo-Electron Tomography
title_fullStr Structural Analysis of HIV-1 Maturation Using Cryo-Electron Tomography
title_full_unstemmed Structural Analysis of HIV-1 Maturation Using Cryo-Electron Tomography
title_short Structural Analysis of HIV-1 Maturation Using Cryo-Electron Tomography
title_sort structural analysis of hiv-1 maturation using cryo-electron tomography
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999899/
https://www.ncbi.nlm.nih.gov/pubmed/21151640
http://dx.doi.org/10.1371/journal.ppat.1001215
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