Proteomics

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


ABSTRACT: The targeting of retroviral Gag polyproteins to the inner leaflet of the plasma membrane is mediated by the N-terminal matrix (MA) domain of Gag. Since retroviruses of different morphogenetic types assemble their immature particles in distinct regions of the host cell, the mechanism of plasma membrane targeting differs between distinct retroviral morphogenetic types. To address this, we have focused on possible mechanistic differences of the MA-plasma membrane targeting of the B type mouse mammary tumor virus (MMTV) and C type HIV-1, which assembles in the cytoplasm and at the plasma membrane, respectively. Molecular dynamic (MD) simulations together with surface mapping have indicated that MMTV uses, similarly to HIV-1, the myristic switch mechanism to anchor the MA to the membrane and electrostatically interacts with phosphatidylinositol 4,5-bisphosphate to stabilize MA orientation. We have observed that the affinity of the MMTV MA to the membrane is lower than the affinity of the HIV 1 MA. This might be related to their different topology and the number of basic residues in the highly basic region, which probably reflects the requirement of C-type retroviruses for tighter membrane binding, essential for the assembly, in contrast to D/B-type retroviruses, assembling in the cytoplasm. Additionally, a comparison of the membrane topology of the HIV-1 MA using the surface mapping method and MD simulations has shown that the residues located at the C-terminus of the HIV-1 MA could be responsible for the stabilization of protein-protein interactions within the HIV-1 MA lattice at the plasma membrane.

INSTRUMENT(S): maXis

ORGANISM(S): Mouse Mammary Tumor Virus Human Immunodeficiency Virus 1

SUBMITTER: Petra Junková  

LAB HEAD: Tomáš Ruml

PROVIDER: PXD018604 | Pride | 2020-05-18

REPOSITORIES: Pride

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

Junková Petra P   Pleskot Roman R   Prchal Jan J   Sýs Jakub J   Ruml Tomáš T  

The Journal of biological chemistry 20200508 26


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 vi  ...[more]

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