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Maturation of the matrix and viral membrane of HIV-1

View ORCID ProfileKun Qu, View ORCID ProfileZunlong Ke, View ORCID ProfileVojtech Zila, Maria Anders-Össwein, Bärbel Glass, Barbara Müller, Hans-Georg Kräusslich, View ORCID ProfileJohn A. G. Briggs
doi: https://doi.org/10.1101/2020.09.23.309542
Kun Qu
1Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, CB2 0QH Cambridge, United Kingdom
2Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany
3Molecular Medicine Partnership Unit, European Molecular Biology Laboratory and Universitätsklinikum Heidelberg, 69117 Heidelberg, Germany
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Zunlong Ke
1Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, CB2 0QH Cambridge, United Kingdom
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Vojtech Zila
4Department of Infectious Diseases, Virology, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany
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Maria Anders-Össwein
4Department of Infectious Diseases, Virology, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany
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Bärbel Glass
4Department of Infectious Diseases, Virology, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany
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Barbara Müller
4Department of Infectious Diseases, Virology, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany
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Hans-Georg Kräusslich
3Molecular Medicine Partnership Unit, European Molecular Biology Laboratory and Universitätsklinikum Heidelberg, 69117 Heidelberg, Germany
4Department of Infectious Diseases, Virology, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany
5German Center for Infection Research, Heidelberg, Germany
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John A. G. Briggs
1Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, CB2 0QH Cambridge, United Kingdom
2Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany
3Molecular Medicine Partnership Unit, European Molecular Biology Laboratory and Universitätsklinikum Heidelberg, 69117 Heidelberg, Germany
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  • For correspondence: jbriggs@mrc-lmb.cam.ac.uk
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Abstract

Gag – the main structural protein of HIV-1 – is recruited to the plasma membrane for virus assembly by its matrix (MA) domain. Gag is subsequently cleaved into its component domains, causing structural maturation to repurpose the virion for cell entry. We determined the structure and arrangement of MA within immature and mature HIV-1, providing a basis to understand MA’s role in virus assembly. Unexpectedly, we found that MA rearranges during maturation, to form a new, hexameric lattice in which the acyl chain of a phospholipid extends out of the membrane to bind a pocket in MA. Our data suggest that proteolytic maturation of HIV-1 not only achieves assembly of the viral capsid surrounding the genome, but extends to repurpose the membrane-bound MA lattice for an entry or post-entry function, and causes partial removal of 2,500 acyl chains from the viral membrane.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted September 23, 2020.
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Maturation of the matrix and viral membrane of HIV-1
Kun Qu, Zunlong Ke, Vojtech Zila, Maria Anders-Össwein, Bärbel Glass, Barbara Müller, Hans-Georg Kräusslich, John A. G. Briggs
bioRxiv 2020.09.23.309542; doi: https://doi.org/10.1101/2020.09.23.309542
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Maturation of the matrix and viral membrane of HIV-1
Kun Qu, Zunlong Ke, Vojtech Zila, Maria Anders-Össwein, Bärbel Glass, Barbara Müller, Hans-Georg Kräusslich, John A. G. Briggs
bioRxiv 2020.09.23.309542; doi: https://doi.org/10.1101/2020.09.23.309542

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