A myristoyl switch at the plasma membrane triggers cleavage and oligomerization of Mason-Pfizer monkey virus matrix protein

  1. Markéta Častorálová
  2. Jakub Sýs
  3. Jan Prchal
  4. Anna Pavlů
  5. Lucie Prokopová
  6. Zina Briki
  7. Martin Hubálek
  8. Tomas Ruml  Is a corresponding author
  1. University of Chemistry and Technology, Czech Republic
  2. Czech Academy of Sciences, Czech Republic

Abstract

For most retroviruses, including HIV, association with the plasma membrane (PM) promotes the assembly of immature particles, which occurs simultaneously with budding and maturation. In these viruses, maturation is initiated by oligomerization of polyprotein precursors. In contrast, several retroviruses, such as Mason-Pfizer monkey virus (M-PMV), assemble in the cytoplasm into immature particles that are transported across the PM. Therefore, protease activation and specific cleavage must not occur until the preassembled particle interacts with the PM. This interaction is triggered by a bipartite signal consisting of a cluster of basic residues in the matrix (MA) domain of Gag polyprotein and a myristoyl moiety N-terminally attached to MA. Here, we provide evidence that myristoyl exposure from the MA core and its insertion into the PM occurs in M-PMV. By a combination of experimental methods, we show that this results in a structural change at the C-terminus of MA allowing efficient cleavage of MA from the downstream region of Gag. This suggests that, in addition to the known effect of the myristoyl switch of HIV-1 MA on the multimerization state of Gag and particle assembly, the myristoyl switch may have a regulatory role in initiating sequential cleavage of M-PMV Gag in immature particles.

Data availability

The data were deposited in Dryad under the DOI: https://doi.org/10.5061/dryad.c59zw3rfn

The following data sets were generated

Article and author information

Author details

  1. Markéta Častorálová

    Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague 6, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  2. Jakub Sýs

    Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague 6, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2589-1631
  3. Jan Prchal

    Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague 6, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3398-5059
  4. Anna Pavlů

    Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague 6, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  5. Lucie Prokopová

    Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague 6, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  6. Zina Briki

    Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague 6, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  7. Martin Hubálek

    Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0247-7956
  8. Tomas Ruml

    Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague 6, Czech Republic
    For correspondence
    tomas.ruml@vscht.cz
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5698-4366

Funding

Grant agency of the Czech Republic (22-19250S)

  • Jan Prchal

Programme Exceles (LX22NPO5103)

  • Jan Prchal

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Mauricio Comas-Garcia, Universidad Autónoma de San Luis Potosí, Mexico

Version history

  1. Received: October 12, 2023
  2. Preprint posted: December 21, 2023 (view preprint)
  3. Accepted: March 10, 2024
  4. Accepted Manuscript published: March 22, 2024 (version 1)
  5. Accepted Manuscript updated: March 27, 2024 (version 2)
  6. Version of Record published: April 12, 2024 (version 3)

Copyright

© 2024, Častorálová et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Markéta Častorálová
  2. Jakub Sýs
  3. Jan Prchal
  4. Anna Pavlů
  5. Lucie Prokopová
  6. Zina Briki
  7. Martin Hubálek
  8. Tomas Ruml
(2024)
A myristoyl switch at the plasma membrane triggers cleavage and oligomerization of Mason-Pfizer monkey virus matrix protein
eLife 13:e93489.
https://doi.org/10.7554/eLife.93489

Share this article

https://doi.org/10.7554/eLife.93489

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