Differences and commonalities in plasma membrane recruitment of the two morphogenetically distinct retroviruses HIV-1 and MMTV.

Autor:	Junková P; Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, Czech Republic; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic., Pleskot R; Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium; VIB Center for Plant Systems Biology, Ghent, Belgium., Prchal J; Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, Czech Republic., Sýs J; Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, Czech Republic., Ruml T; Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, Czech Republic. Electronic address: tomas.ruml@vscht.cz.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2020 Jun 26; Vol. 295 (26), pp. 8819-8833. Date of Electronic Publication: 2020 May 08.
DOI:	10.1074/jbc.RA119.011991
Abstrakt:	Retroviral Gag polyproteins are targeted to the inner leaflet of the plasma membrane through their N-terminal matrix (MA) domain. Because retroviruses of different morphogenetic types assemble their immature particles in distinct regions of the host cell, the mechanism of MA-mediated plasma membrane targeting differs among distinct retroviral morphogenetic types. Here, we focused on possible mechanistic differences of the MA-mediated plasma membrane targeting of the B-type mouse mammary tumor virus (MMTV) and C-type HIV-1, which assemble in the cytoplasm and at the plasma membrane, respectively. Molecular dynamics simulations, together with surface mapping, indicated that, similarly to HIV-1, MMTV uses a myristic switch to anchor the MA to the membrane and electrostatically interacts with phosphatidylinositol 4,5-bisphosphate to stabilize MA orientation. We observed that the affinity of MMTV MA to the membrane is lower than that of HIV-1 MA, possibly related to their different topologies and the number of basic residues in the highly basic MA region. The latter probably reflects the requirement of C-type retroviruses for tighter membrane binding, essential for assembly, unlike for D/B-type retroviruses, which assemble in the cytoplasm. A comparison of the membrane topology of the HIV-1 MA, using the surface-mapping method and molecular dynamics simulations, revealed that the residues at the HIV-1 MA C terminus help stabilize protein-protein interactions within the HIV-1 MA lattice at the plasma membrane. In summary, HIV-1 and MMTV share common features such as membrane binding of the MA via hydrophobic interactions and exhibit several differences, including lower membrane affinity of MMTV MA. Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article. (© 2020 Junková et al.)
Databáze:	MEDLINE
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