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

0585463 - ÚOCHB 2025 RIV GB eng J - Journal Article
Častorálová, M. - Sýs, Jakub - Prchal, J. - Pavlů, A. - Prokopová, L. - Briki, Z. - Hubálek, Martin - Ruml, T.
A myristoyl switch at the plasma membrane triggers cleavage and oligomerization of Mason-Pfizer monkey virus matrix protein.
eLife. Roč. 13, March (2024), č. článku e93489. ISSN 2050-084X. E-ISSN 2050-084X
R&D Projects: GA MŠMT(CZ) LX22NPO5103; GA ČR(CZ) GA22-19250S
Institutional support: RVO:61388963
Keywords : hiv-1 gag * type-1 gag * myristoyl switch * betaretrovirus * matrix protein * protease * maturation * Viruses
Impact factor: 7.7, year: 2022
Method of publishing: Open access
https://doi.org/10.7554/eLife.93489

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 pre-assembled 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.
Permanent Link: https://hdl.handle.net/11104/0353250